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17 pages, 5539 KiB

Open AccessArticle

Carbon Nanofiber—Sodium Alginate Composite Aerogels Loaded with Vitamin D: The Cytotoxic and Apoptotic Effects on Colon Cancer Cells

by Ozlem Bingol Ozakpinar, Havva Dastan, Merve Gurboga, Fatih Serdar Sayin, Derya Ozsavci and Elif Caliskan Salihi

Gels 2023, 9(7), 561; https://doi.org/10.3390/gels9070561 - 10 Jul 2023

Cited by 1 | Viewed by 1322

Abstract

Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer and the third leading cause of cancer-related deaths worldwide. A substantial body of literature supports the crucial role of vitamin D (VD) in the etiology, progression, prognosis, and treatment of cancer. Recent clinical [...] Read more.

Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer and the third leading cause of cancer-related deaths worldwide. A substantial body of literature supports the crucial role of vitamin D (VD) in the etiology, progression, prognosis, and treatment of cancer. Recent clinical studies have found an inverse correlation between CRC incidence and serum VD levels. However, the low water solubility of VD and its anticarcinogenic activity at supraphysiological plasma levels, which causes hypercalcemia, required carrier systems. Carbon-based nanomaterials are excellent eco-friendly candidates, with exceptional chemical resistance, efficient mechanical properties, and negligible weight. Furthermore, composite aerogels manufactured from these nanomaterials have gained interest due to their extensive surface areas and porous structures, which make them suitable for delivering drugs. Our research aimed to study the development of composite aerogels loaded with VD by utilizing carbon nanofibers (CNFs) in an aerogel matrix provided to colon cancer cells. For this purpose, Aero1 as a drug delivery system was first prepared and characterized using XRD, FTIR, and SEM methods. Biochemical methods were employed to evaluate the antiproliferative, apoptotic, and anti-migratory effects on colon cancer cells. FTIR and XRD measurements confirmed the production of aerogels. SEM analysis revealed that aerogels have a non-uniform surface. The findings showed that aerogels can effectively deliver VD to the colon cancer cells, while also inhibiting cancer cell proliferation and migration. This research suggests that the Aero1 drug delivery system could be a valuable tool in the fight against colon cancer and other health issues. Full article

(This article belongs to the Special Issue Advanced Gels for Drug Delivery Systems Based on Sustainable Development Goals (SDGs))

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22 pages, 6199 KiB

Open AccessArticle

Lincomycin HCl-Loaded Borneol-Based In Situ Gel for Periodontitis Treatment

by Napaphol Puyathorn, Nutdanai Lertsuphotvanit, Takron Chantadee, Wiwat Pichayakorn and Thawatchai Phaechamud

Gels 2023, 9(6), 495; https://doi.org/10.3390/gels9060495 - 19 Jun 2023

Cited by 2 | Viewed by 1249

Abstract

Solvent exchange-induced in situ forming gel (ISG) has emerged as a versatile drug delivery system, particularly for periodontal pocket applications. In this study, we developed lincomycin HCl-loaded ISGs using a 40% borneol-based matrix and N-methyl pyrrolidone (NMP) as a solvent. The physicochemical properties [...] Read more.

Solvent exchange-induced in situ forming gel (ISG) has emerged as a versatile drug delivery system, particularly for periodontal pocket applications. In this study, we developed lincomycin HCl-loaded ISGs using a 40% borneol-based matrix and N-methyl pyrrolidone (NMP) as a solvent. The physicochemical properties and antimicrobial activities of the ISGs were evaluated. The prepared ISGs exhibited low viscosity and reduced surface tension, allowing for easy injection and spreadability. Gel formation increased the contact angle on agarose gel, while higher lincomycin HCl content decreased water tolerance and facilitated phase separation. The drug-loading influenced solvent exchange and matrix formation, resulting in thinner and inhomogeneous borneol matrices with slower gel formation and lower gel hardness. The lincomycin HCl-loaded borneol-based ISGs demonstrated sustained drug release above the minimum inhibitory concentration (MIC) for 8 days, following Fickian diffusion and fitting well with Higuchi’s equation. These formulations exhibited dose-dependent inhibition of Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 8739, and Prophyromonas gingivalis ATCC 33277, and the release of NMP effectively inhibited Candida albicans ATCC 10231. Overall, the 7.5% lincomycin HCl-loaded 40% borneol-based ISGs hold promise as localized drug delivery systems for periodontitis treatment. Full article

(This article belongs to the Special Issue Advanced Gels for Drug Delivery Systems Based on Sustainable Development Goals (SDGs))

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21 pages, 3796 KiB

Open AccessArticle

Clotrimazole-Loaded Borneol-Based In Situ Forming Gel as Oral Sprays for Oropharyngeal Candidiasis Therapy

by Nutdanai Lertsuphotvanit, Sarun Tuntarawongsa, Kritamorn Jitrangsri and Thawatchai Phaechamud

Gels 2023, 9(5), 412; https://doi.org/10.3390/gels9050412 - 15 May 2023

Cited by 3 | Viewed by 1673

Abstract

Oral candidiasis encompasses fungal infections of the tongue and other oral mucosal sites with fungal overgrowth and its invasion of superficial oral tissues. Borneol was assessed in this research as the matrix-forming agent of clotrimazole-loaded in situ forming gel (ISG) comprising clove oil [...] Read more.

Oral candidiasis encompasses fungal infections of the tongue and other oral mucosal sites with fungal overgrowth and its invasion of superficial oral tissues. Borneol was assessed in this research as the matrix-forming agent of clotrimazole-loaded in situ forming gel (ISG) comprising clove oil as the co-active agent and N-methyl pyrrolidone (NMP) as a solvent. Their physicochemical properties, including pH, density, viscosity, surface tension, contact angle, water tolerance, gel formation, and drug release/permeation, were determined. Their antimicrobial activities were tested using agar cup diffusion. The pH values of clotrimazole-loaded borneol-based ISGs were in the range of 5.59–6.61, which are close to the pH of 6.8 of saliva. Increasing the borneol content in the formulation slightly decreased the density, surface tension, water tolerance, and spray angle but increased the viscosity and gel formation. The borneol matrix formation from NMP removal promoted a significantly (p < 0.05) higher contact angle of the borneol-loaded ISGs on agarose gel and porcine buccal mucosa than those of all borneol-free solutions. Clotrimazole-loaded ISG containing 40% borneol demonstrated appropriate physicochemical properties and rapid gel formation at microscopic and macroscopic levels. In addition, it prolonged drug release with a maximum flux of 370 µg·cm⁻² at 2 days. The borneol matrix generated from this ISG obsentively controlled the drug penetration through the porcine buccal membrane. Most clotrimazole amounts still remained in formulation at the donor part and then the buccal membrane and receiving medium, repectively. Therefore, the borneol matrix extended the drug release and penetration through the buccal membrane efficiently. Some accumulated clotrimazole in tissue should exhibit its potential antifugal activity against microbes invading the host tissue. The other predominant drug release into the saliva of the oral cavity should influence the pathogen of oropharyngeal candidiasis. Clotrimazole-loaded ISG demonstrated efficacious inhibition of growth against S. aureus, E. coli, C. albicans, C. krusei, C. Lusitaniae, and C. tropicalis. Consequently, the clotrimazole-loaded ISG exhibited great potential as a drug delivery system for oropharyngeal candidiasis treatment by localized spraying. Full article

(This article belongs to the Special Issue Advanced Gels for Drug Delivery Systems Based on Sustainable Development Goals (SDGs))

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14 pages, 3641 KiB

Open AccessArticle

Biocompatible Glycol Chitosan Microgels as Effective Drug Carriers

by Mehtap Sahiner, Aynur S. Yilmaz, Ramesh S. Ayyala and Nurettin Sahiner

Gels 2023, 9(5), 398; https://doi.org/10.3390/gels9050398 - 10 May 2023

Cited by 5 | Viewed by 1487

Abstract

Glycol chitosan (GC) is a chitosan (CH) derivative with improved water solubility with regards to CH which affords significant solubility advantages. In this study, microgels of GC as p(GC) were synthesized by a microemulsion technique at various crosslinking ratios e.g., 5%, 10%, 50%, [...] Read more.

Glycol chitosan (GC) is a chitosan (CH) derivative with improved water solubility with regards to CH which affords significant solubility advantages. In this study, microgels of GC as p(GC) were synthesized by a microemulsion technique at various crosslinking ratios e.g., 5%, 10%, 50%, 75%, and 150% based on the repeating unit of GC using divinyl sulfone (DVS) as a crosslinker. The prepared p(GC) microgels were tested for blood compatibility and it was found that p(GC) microgels at 1.0 mg/mL concentration possessed a 1.15 ± 0.1% hemolysis ratio and 89 ± 5% blood clotting index value confirming their hemocompatibility. In addition, p(GC) microgels were found biocompatible with 75.5 ± 5% cell viability against L929 fibroblasts even at a 2.0 mg/mL concentration. By loading and releasing tannic acid (TA) (a polyphenolic compound with high antioxidant activity) as an active agent, p(GC) microgels’ possible drug delivery device application was examined. The TA loading amount of p(GC) microgels was determined as 323.89 mg/g, and TA releases from TA loaded microgels (TA@p(GC)) were found to be linear within 9 h and a total amount of TA released was determined as 42.56 ± 2 mg/g within 57 h. According to the Trolox equivalent antioxidant capacity (TEAC) test, 400 µL of the sample added to the ABTS+ solution inhibited 68.5 ± 1.7% of the radicals. On the other hand, the total phenol content (FC) test revealed that 2000 μg/mL of TA@p(GC) microgels resulted in 27.5 ± 9.5 mg/mL GA eq antioxidant properties. Full article

(This article belongs to the Special Issue Advanced Gels for Drug Delivery Systems Based on Sustainable Development Goals (SDGs))

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12 pages, 455 KiB

Open AccessArticle

The Effect of Hyaluronic Acid Gel on Periodontal Parameters, Pro-Inflammatory Cytokines and Biochemical Markers in Periodontitis Patients

by Chenar Anwar Mohammad, Barzan Abdulwahab Mirza, Zainab Salim Mahmood and Faraedon Mostafa Zardawi

Gels 2023, 9(4), 325; https://doi.org/10.3390/gels9040325 - 12 Apr 2023

Cited by 4 | Viewed by 2296

Abstract

Hyaluronic acid in its various forms shows bacteriostatic, fungistatic, anti-inflammatory, anti-edematous, osteoinductive, and pro-angiogenetic properties. This study aimed to evaluate the effect of subgingival delivery of 0.8% hyaluronic acid (HA) gel on clinical periodontal parameters, pro-inflammatory cytokines (IL-1 beta and TNF-alpha) and biochemical [...] Read more.

Hyaluronic acid in its various forms shows bacteriostatic, fungistatic, anti-inflammatory, anti-edematous, osteoinductive, and pro-angiogenetic properties. This study aimed to evaluate the effect of subgingival delivery of 0.8% hyaluronic acid (HA) gel on clinical periodontal parameters, pro-inflammatory cytokines (IL-1 beta and TNF-alpha) and biochemical markers of inflammation (C-reactive protein (CRP) and alkaline phosphatase (ALP) enzymes) in patients with periodontitis. Seventy-five patients with chronic periodontitis were divided randomly into three groups (25 in each group): group I received scaling and surface root debridement (SRD) + HA gel; group II received SRD + chlorhexidine gel; and group III received surface root debridement alone. Clinical periodontal parameter measurements and blood samples were collected to estimate pro-inflammatory and biochemical parameters at the baseline before therapy and after two months of therapy. The results show that HA gel has a significant effect on the reduction in clinical periodontal parameters (PI, GI, BOP, PPD, and CAL), IL-1 beta, TNF-alpha, CRP, and ALP after 2 months of therapy as compared to the baseline (p < 0.05) with nonsignificant differences from the CHX group (p > 0.05), except GI (p < 0.05), and significant differences from the SRD group (p < 0.05). Moreover, significant differences were found between the three groups regarding the mean improvements of GI, BOP, PPD, IL-1β, CRP, and ALP. It can be concluded that HA gel has a positive effect on clinical periodontal parameters and improvements in inflammatory mediators similar to chlorhexidine. Therefore, HA gel can be used as an adjuvant to SRD in the treatment of periodontitis. Full article

(This article belongs to the Special Issue Advanced Gels for Drug Delivery Systems Based on Sustainable Development Goals (SDGs))

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26 pages, 1870 KiB

Open AccessArticle

Vaginal Sheets with Thymbra capitata Essential Oil for the Treatment of Bacterial Vaginosis: Design, Characterization and In Vitro Evaluation of Efficacy and Safety

by Mariana Tomás, Lúcia G. V. Sousa, Ana Sofia Oliveira, Carolina P. Gomes, Ana Palmeira-de-Oliveira, Carlos Cavaleiro, Lígia Salgueiro, Nuno Cerca, José Martinez-de-Oliveira and Rita Palmeira-de-Oliveira

Gels 2023, 9(4), 293; https://doi.org/10.3390/gels9040293 - 02 Apr 2023

Cited by 1 | Viewed by 2384

Abstract

We aimed to incorporate Thymbra capitata essential oil (TCEO), a potent antimicrobial natural product against bacterial vaginosis (BV)-related bacteria, in a suitable drug delivery system. We used vaginal sheets as dosage form to promote immediate relief of the typical abundant vaginal discharge with [...] Read more.

We aimed to incorporate Thymbra capitata essential oil (TCEO), a potent antimicrobial natural product against bacterial vaginosis (BV)-related bacteria, in a suitable drug delivery system. We used vaginal sheets as dosage form to promote immediate relief of the typical abundant vaginal discharge with unpleasant odour. Excipients were selected to promote the healthy vaginal environment reestablishment and bioadhesion of formulations, while the TCEO acts directly on BV pathogens. We characterized vaginal sheets with TCEO in regard to technological characterization, predictable in vivo performance, in vitro efficacy and safety. Vaginal sheet D.O (acid lactic buffer, gelatine, glycerine, chitosan coated with TCEO 1% w/w) presented a higher buffer capacity and ability to absorb vaginal fluid simulant (VFS) among all vaginal sheets with EO, showing one of the most promising bioadhesive profiles, an excellent flexibility and structure that allow it to be easily rolled for application. Vaginal sheet D.O with 0.32 µL/mL TCEO was able to significantly reduce the bacterial load of all in vitro tested Gardnerella species. Although vaginal sheet D.O presented toxicity at some concentrations, this product was developed for a short time period of treatment, so this toxicity can probably be limited or even reversed when the treatment ends. Full article

(This article belongs to the Special Issue Advanced Gels for Drug Delivery Systems Based on Sustainable Development Goals (SDGs))

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21 pages, 4208 KiB

Open AccessArticle

Development and Evaluation of Essential Oil-Based Nanoemulgel Formulation for the Treatment of Oral Bacterial Infections

by Niamat Ullah, Adnan Amin, Arshad Farid, Samy Selim, Sheikh Abdur Rashid, Muhammad Imran Aziz, Sairah Hafeez Kamran, Muzammil Ahmad Khan, Nauman Rahim Khan, Saima Mashal and Muhammad Mohtasheemul Hasan

Gels 2023, 9(3), 252; https://doi.org/10.3390/gels9030252 - 21 Mar 2023

Cited by 6 | Viewed by 3773

Abstract

Prevalence of oral infections in diabetic patients is a health challenge due to persistent hyperglycemia. However, despite great concerns, limited treatment options are available. We therefore aimed to develop nanoemulsion gel (NEG) for oral bacterial infections based on essential oils. Clove and cinnamon [...] Read more.

Prevalence of oral infections in diabetic patients is a health challenge due to persistent hyperglycemia. However, despite great concerns, limited treatment options are available. We therefore aimed to develop nanoemulsion gel (NEG) for oral bacterial infections based on essential oils. Clove and cinnamon essential oils based nanoemulgel were prepared and characterized. Various physicochemical parameters of optimized formulation including viscosity (65311 mPa·S), spreadability (36 g·cm/s), and mucoadhesive strength 42.87 N/cm²) were within prescribed limits. The drug contents of the NEG were 94.38 ± 1.12% (cinnamaldehyde) and 92.96 ± 2.08% (clove oil). A significant concentration of clove (73.9%) and cinnamon essential oil (71.2 %) was released from a polymer matrix of the NEG till 24 h. The ex vivo goat buccal mucosa permeation profile revealed a significant (52.7–54.2%) permeation of major constituents which occurred after 24 h. When subjected to antimicrobial testing, significant inhibition was observed for several clinical strains, namely Staphylococcus aureus (19 mm), Staphylococcus epidermidis (19 mm), and Pseudomonas aeruginosa (4 mm), as well as against Bacillus chungangensis (2 mm), whereas no inhibition was detected for Bacillus paramycoides and Paenibacillus dendritiformis when NEG was utilized. Likewise promising antifungal (Candida albicans) and antiquorum sensing activities were observed. It was therefore concluded that cinnamon and clove oil-based NEG formulation presented significant antibacterial-, antifungal, and antiquorum sensing activities. Full article

(This article belongs to the Special Issue Advanced Gels for Drug Delivery Systems Based on Sustainable Development Goals (SDGs))

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20 pages, 4914 KiB

Open AccessArticle

Qbd-Based Approach to Optimize Niosomal Gel of Levosulpiride for Transdermal Drug Delivery

by Ahmed S. Alnaim, Hiral Shah, Anroop B. Nair, Vivek Mewada, Smit Patel, Shery Jacob, Bandar Aldhubiab, Mohamed A. Morsy, Rashed M. Almuqbil, Pottathil Shinu and Jigar Shah

Gels 2023, 9(3), 213; https://doi.org/10.3390/gels9030213 - 10 Mar 2023

Cited by 3 | Viewed by 1864

Abstract

Poor aqueous solubility besides extensive hepatic first effect significantly decreases the oral absorption of levosulpiride, which in turn minimizes its therapeutic effectiveness. Niosomes have been extensively investigated as a transdermal vesicular nanocarrier to increase the delivery of low permeable compounds into and across [...] Read more.

Poor aqueous solubility besides extensive hepatic first effect significantly decreases the oral absorption of levosulpiride, which in turn minimizes its therapeutic effectiveness. Niosomes have been extensively investigated as a transdermal vesicular nanocarrier to increase the delivery of low permeable compounds into and across the skin. This research work was to design, develop and optimize levosulpiride-loaded niosomal gel and to evaluate its prospects for transdermal delivery. The Box-Behnken design was used to optimize niosomes by analyzing the impact of three factors (cholesterol; X₁, Span 40; X₂, and sonication time; X₃) on the responses (particle size, Y₁, and entrapment efficiency, Y₂). Optimized formulation (NC) was incorporated into gel and evaluated for pharmaceutical properties, drug release study, ex vivo permeation, and in vivo absorption. The design experiment data suggest that all three independent variables influence both response variables significantly (p < 0.01). Pharmaceutical characteristics of NC vesicles showed the absence of drug excipient interaction, nanosize (~102.2 nm), narrow distribution (~0.218), adequate zeta potential (−49.9 mV), and spherical shape, which are suitable for transdermal therapy. The levosulpiride release rates varied significantly (p < 0.01) between niosomal gel formulation and control. Greater flux (p < 0.01) was observed with levosulpiride-loaded niosomal gel than with control gel formulation. Indeed, the drug plasma profile of niosomal gel was significantly higher (p < 0.005), with ~3 folds higher C_max and greater bioavailability (~500% higher; p < 0.0001) than its counterpart. Overall, these findings imply that the use of an optimized niosomal gel formulation can increase the therapeutic efficacy of levosulpiride and may represent a promising alternative to conventional therapy. Full article

(This article belongs to the Special Issue Advanced Gels for Drug Delivery Systems Based on Sustainable Development Goals (SDGs))

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19 pages, 2635 KiB

Open AccessArticle

Calcitermin-Loaded Smart Gels Activity against Candida albicans: A Preliminary In Vitro Study

by Denise Bellotti, Maria D’Accolti, Walter Pula, Nicolas Huang, Fanny Simeliere, Elisabetta Caselli, Elisabetta Esposito and Maurizio Remelli

Gels 2023, 9(2), 165; https://doi.org/10.3390/gels9020165 - 18 Feb 2023

Cited by 4 | Viewed by 1490

Abstract

Calcitermin is an antimicrobial peptide of 15 amino acids found in human nasal fluid characterized by antifungal and antibacterial properties. Candida albicans is the most common human fungal pathogen affecting many tissues, such as vaginal mucosa. In this study a formulation suitable for [...] Read more.

Calcitermin is an antimicrobial peptide of 15 amino acids found in human nasal fluid characterized by antifungal and antibacterial properties. Candida albicans is the most common human fungal pathogen affecting many tissues, such as vaginal mucosa. In this study a formulation suitable for calcitermin administration on vaginal mucosa was developed for the treatment of fungal infections. To favor topical application, mucosal adhesion, and permanence, gels based on poloxamer 407 and xanthan gum were designed and compared with regard to their rheological behavior, erosion, and leakage. The selected gel was loaded with calcitermin, whose release kinetic was evaluated in vitro by Franz cells. An antifungal activity assay was conducted to assess the calcitermin anticandidal potential and the effect of its inclusion in the selected gel. The rheological study revealed the elastic and viscous moduli behavior as a function of poloxamer 407 and xanthan gum concentration. Xanthan gum presence decreased the transition temperature of the gel, while prolonging its erosion and leakage. Particularly, poloxamer 407, 18% and xanthan gum 0.4% were chosen. The calcitermin loading in the selected gel resulted in a transparent and homogeneous formulation and in a 4-fold decrease of the release rate with respect to the calcitermin solution, as evidenced by Franz cell study. The anticandidal activity tests demonstrated that calcitermin-loaded gel was more active against Candida albicans with respect to the peptide solution. Full article

(This article belongs to the Special Issue Advanced Gels for Drug Delivery Systems Based on Sustainable Development Goals (SDGs))

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14 pages, 2033 KiB

Open AccessArticle

Development of a Polyherbal Topical Gel for the Treatment of Acne

by Benedict Jose Chellathurai, Ramyadevi Anburose, Mohammad H. Alyami, Mohan Sellappan, Mohammad F. Bayan, Balakumar Chandrasekaran, Kumarappan Chidambaram and Mohamed Rahamathulla

Gels 2023, 9(2), 163; https://doi.org/10.3390/gels9020163 - 17 Feb 2023

Cited by 6 | Viewed by 3483

Abstract

The present work aimed to formulate and evaluate a polyherbal gel using Aloe barbadensis and extract of Vigna radiata for the treatment of acne, a disorder of the skin in which hair follicles and sebaceous glands are blocked, causing inflammation and redness of [...] Read more.

The present work aimed to formulate and evaluate a polyherbal gel using Aloe barbadensis and extract of Vigna radiata for the treatment of acne, a disorder of the skin in which hair follicles and sebaceous glands are blocked, causing inflammation and redness of the skin. Aloe barbadensis pulp was collected and mixed with the extract of Vigna radiata and formulated into a gel using Carbopol 940, triethanolamine, and propylene glycol as the gelling agent, viscosity modifier, and pH modifier, respectively. The gel was evaluated for its antimicrobial properties against Staphylococcus aureus, Escherichia coli, and Candida albicans. Antimicrobial agents, such as gentamycin and fluconazole, were used as the standards. The developed formulation showed promising zone of inhibition. The gel was further evaluated for its physicochemical properties. The formulation showed a promising effect on acne together with the additive effect of Aloe barbadensis on skin. Full article

(This article belongs to the Special Issue Advanced Gels for Drug Delivery Systems Based on Sustainable Development Goals (SDGs))

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22 pages, 3388 KiB

Open AccessArticle

Intranasal Administration of Dolutegravir-Loaded Nanoemulsion-Based In Situ Gel for Enhanced Bioavailability and Direct Brain Targeting

by Anroop B. Nair, Sunita Chaudhary, Shery Jacob, Dhwani Patel, Pottathil Shinu, Hiral Shah, Ankit Chaudhary, Bandar Aldhubiab, Rashed M. Almuqbil, Ahmed S. Alnaim, Fatemah Alqattan and Jigar Shah

Gels 2023, 9(2), 130; https://doi.org/10.3390/gels9020130 - 03 Feb 2023

Cited by 7 | Viewed by 2220

Abstract

Dolutegravir’s therapeutic effectiveness in the management of neuroAIDS is mainly limited by its failure to cross the blood–brain barrier. However, lipid-based nanovesicles such as nanoemulsions have demonstrated their potential for the brain targeting of various drugs by intranasal delivery. Thus, the purpose of [...] Read more.

Dolutegravir’s therapeutic effectiveness in the management of neuroAIDS is mainly limited by its failure to cross the blood–brain barrier. However, lipid-based nanovesicles such as nanoemulsions have demonstrated their potential for the brain targeting of various drugs by intranasal delivery. Thus, the purpose of this study was to develop a Dolutegravir-loaded nanoemulsion-based in situ gel and evaluate its prospective for brain targeting by intranasal delivery. Dolutegravir-loaded nanoemulsions were prepared using dill oil, Tween^® 80, and Transcutol^® P. Optimization of the nanoemulsion particle size and drug release was carried out using a simplex lattice design. Formulations (F1–F7 and B1–B6) were assessed for various pharmaceutical characteristics. Ex vivo permeation and ciliotoxicity studies of selected in situ gels (B1) were conducted using sheep nasal mucosa. Drug targeting to the brain was assessed in vivo in rats following the nasal delivery of B1. The composition of oil, surfactant, and cosurfactant significantly (p < 0.05) influenced the dependent variables (particle size and % of drug release in 8 h). Formulation B1 exhibits pharmaceutical characteristics that are ideal for intranasal delivery. The mucosal steady-state flux noticed with BI was significantly greater (p < 0.005) than for the control gel. A histopathology of nasal mucosa treated with BI showed no signs of toxicity or cellular damage. Intranasal administration of B1 resulted in greater C_max (~six-fold, p < 0.0001) and AUC_0−α (~five-fold, p < 0.0001), and decreased T_max (1 h) values in the brain, compared to intravenous administration. Meantime, the drug level in the plasma was relatively low, suggesting less systemic exposure to Dolutegravir through intranasal delivery. In summary, the promising data observed here signifies the prospective of B1 to enhance the brain targeting of Dolutegravir by intranasal delivery and it could be used as a feasible and practicable strategy for the management of neuroAIDS. Full article

(This article belongs to the Special Issue Advanced Gels for Drug Delivery Systems Based on Sustainable Development Goals (SDGs))

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28 pages, 9868 KiB

Open AccessArticle

Physicochemical and Bioactivity Characteristics of Doxycycline Hyclate-Loaded Solvent Removal-Induced Ibuprofen-Based In Situ Forming Gel

by Napaphol Puyathorn, Setthapong Senarat, Nutdanai Lertsuphotvanit and Thawatchai Phaechamud

Gels 2023, 9(2), 128; https://doi.org/10.3390/gels9020128 - 03 Feb 2023

Cited by 9 | Viewed by 2379

Abstract

Modulation with the suppression of infection and inflammation is essential to the successful treatment of periodontitis. An aqueous insoluble hydrophobic anti-inflammatory compound, i.e., ibuprofen (IBU), was investigated in this study as the matrix-forming agent of a doxycycline hyclate (DH)-loaded solvent removal-induced in situ [...] Read more.

Modulation with the suppression of infection and inflammation is essential to the successful treatment of periodontitis. An aqueous insoluble hydrophobic anti-inflammatory compound, i.e., ibuprofen (IBU), was investigated in this study as the matrix-forming agent of a doxycycline hyclate (DH)-loaded solvent removal-induced in situ forming gel (ISG) using dimethyl sulfoxide (DMSO) and N-methyl pyrrolidone (NMP) as the solvents. Their physicochemical properties, including pH, density, viscosity, surface tension, contact angle, water tolerance, injectability, mechanical properties, gel formation, and drug release, were determined. Their antimicrobial activities were tested using agar cup diffusion, and their anti-inflammatory activity was assessed using thermal inhibition of protein denaturation of egg albumin. Increasing the IBU content decreased the density, pH, surface tension, and contact angle but increased the viscosity, force and work of injection, and gel formation of IBU-based ISG solution. Although their water tolerance values decreased with the increase in IBU content, the addition of DH and the use of NMP led to high water tolerance. The characterization of the dried gel remnants of ISGs presented no change in IBU crystallinity and thermal properties and confirmed no chemical interaction among the components of ISGs. The obtained transformed IBU matrix prolonged the release of DH and IBU from ISGs over 7 days from its tortuously packed IBU matrix with small pores, and conformed well with Fickian diffusion mechanism. The developed DH-loaded solvent removal-induced IBU-based ISGs exhibited efficient antimicrobial activities against Staphylococcus aureus, methicillin-resistant S. aureus, Escherichia coli, Candida albicans, Porphyromonas gingivalis, and Aggregatibacter actinomycetemcomitans. IBU in formulation promoted the antimicrobial activity of ISGs, whereas DH and NMP promoted the anti-inflammatory activity of ISGs. Consequently, the DH-loaded solvent removal-induced IBU-based ISGs proposed in this study show great potential as an effective bioactive drug delivery system for periodontitis treatment by localized periodontal pocket injection. Full article

(This article belongs to the Special Issue Advanced Gels for Drug Delivery Systems Based on Sustainable Development Goals (SDGs))

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17 pages, 1616 KiB

Open AccessArticle

Poly(Sulfobetaine Methacrylate-co-Vinyl Pyrrolidone) Hydrogels as Potential Contact Lenses Delivery Systems for Timolol Maleate

by Denitsa Nikolova, Christo Tzachev, Lachezar Christov and Elena Vassileva

Gels 2023, 9(2), 114; https://doi.org/10.3390/gels9020114 - 30 Jan 2023

Cited by 1 | Viewed by 1606

Abstract

The study reveals the development of novel hydrogels based on sulfobetaine methacrylate (SB) and vinyl pyrrolidone (VP) copolymers as potential contact lenses delivery systems of timolol maleate (TM). The novel copolymer networks demonstrated composition dependent swelling kinetics, where the hydrophilicity of VP and [...] Read more.

The study reveals the development of novel hydrogels based on sulfobetaine methacrylate (SB) and vinyl pyrrolidone (VP) copolymers as potential contact lenses delivery systems of timolol maleate (TM). The novel copolymer networks demonstrated composition dependent swelling kinetics, where the hydrophilicity of VP and the physical network of SB monomeric units play significant roles. TM loading efficiency appeared to slightly depend on the copolymeric composition, increasing upon VP monomeric unit increase. In contrast, the TM release was prolonged when the SB monomeric units content in the copolymers increased, reaching full drug release for 48 h for the SB-rich networks. The transparency of the hydrogels was also studied and the obtained values demonstrate their applicability as potential materials for soft contact lenses. The study has revealed the potential of these novel copolymeric hydrogels as materials for contact lenses delivery systems of timolol maleate. Full article

(This article belongs to the Special Issue Advanced Gels for Drug Delivery Systems Based on Sustainable Development Goals (SDGs))

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24 pages, 7384 KiB

Open AccessArticle

Development and Evaluation of Cellulose Derivative and Pectin Based Swellable pH Responsive Hydrogel Network for Controlled Delivery of Cytarabine

by Nighat Batool, Rai Muhammad Sarfraz, Asif Mahmood, Umaira Rehman, Muhammad Zaman, Shehla Akbar, Diena M. Almasri and Heba A. Gad

Gels 2023, 9(1), 60; https://doi.org/10.3390/gels9010060 - 12 Jan 2023

Cited by 6 | Viewed by 2125

Abstract

In the present study, pH-sensitive, biodegradable, and biocompatible Na-CMC/pectin poly(methacrylic acid) hydrogels were synthesized using an aqueous free radical polymerization technique and encapsulated by cytarabine (anti-cancer drug). The aim of the project was to sustain the plasma profile of cytarabine through oral administration. [...] Read more.

In the present study, pH-sensitive, biodegradable, and biocompatible Na-CMC/pectin poly(methacrylic acid) hydrogels were synthesized using an aqueous free radical polymerization technique and encapsulated by cytarabine (anti-cancer drug). The aim of the project was to sustain the plasma profile of cytarabine through oral administration. Sodium carboxymethyl cellulose (Na-CMC) and pectin were cross-linked chemically with methacrylic acid (MAA) as a monomer, using methylene bisacrylamide (MBA) as cross-linker and ammonium per sulfate (APS) as an initiator. Prepared hydrogel formulations were characterized for their texture, morphology, cytarabine loading efficiency, compositional and structural properties, thermal nature, stability, swelling response, drug release profile (pH 1.2 and pH 7.4), and in-vivo pharmacokinetic evaluation. Cytarabine-loaded hydrogels were also evaluated for their safety profile by carrying out toxicity studies in rabbits. Results demonstrated efficient encapsulation of cytarabine into the prepared network with loading ranging from 48.5–82.3%. The highest swelling ratio of 39.38 and maximum drug release of 83.29–85.27% were observed at pH 7.4, highlighting the pH responsiveness of the grafted system. Furthermore, cytarabine maximum release was noticed over 24 h, ensuring a sustained release response for all formulations. Histopathological studies and hemolytic profiles confirmed that the prepared hydrogel system was safe, biocompatible, and non-irritant, showing no symptoms of any toxicities and degeneration in organs. Moreover, pharmacokinetic estimation of the cytarabine-loaded hydrogel showed a remarkable increase in the plasma half-life from 4.44 h to 9.24 h and AUC from 22.06 μg/mL.h to 56.94 μg/mL.h. This study revealed that the prepared hydrogel carrier system has excellent abilities in delivering the therapeutic moieties in a controlled manner. Full article

(This article belongs to the Special Issue Advanced Gels for Drug Delivery Systems Based on Sustainable Development Goals (SDGs))

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12 pages, 2372 KiB

Open AccessArticle

Phenol-Grafted Alginate Sulfate Hydrogel as an Injectable FGF-2 Carrier

by Ryota Goto, Masaki Nakahata and Shinji Sakai

Gels 2022, 8(12), 818; https://doi.org/10.3390/gels8120818 - 12 Dec 2022

Cited by 1 | Viewed by 2133

Abstract

In the field of tissue engineering, fibroblast growth factor-2 (FGF-2) effectively regenerates damaged tissue and restores its biological function. However, FGF-2 readily diffuses and degrades under physiological conditions. Therefore, methods for the sustained and localized delivery of FGF-2 are needed. Drug delivery systems [...] Read more.

In the field of tissue engineering, fibroblast growth factor-2 (FGF-2) effectively regenerates damaged tissue and restores its biological function. However, FGF-2 readily diffuses and degrades under physiological conditions. Therefore, methods for the sustained and localized delivery of FGF-2 are needed. Drug delivery systems using hydrogels as carriers have attracted significant interest. Injectable hydrogels with an affinity for FGF-2 are candidates for FGF-2 delivery systems. In this study, we fabricated a hydrogel from phenol-grafted alginate sulfate (AlgS-Ph) and investigated its application to the delivery of FGF-2. The hydrogel was prepared under mild conditions via horseradish peroxidase (HRP)-mediated cross-linking. Surface plasmon resonance (SPR) measurements show that the AlgS-Ph hydrogel has an affinity for FGF-2 in accordance with its degree of sulfation. Conditions for the preparation of the AlgS-Ph hydrogel, including HRP and H₂O₂ concentrations, are optimized so that the hydrogel can be used as an injectable drug carrier. The hydrogel shows no cytotoxicity when using 10T1/2 cells as a model cell line. The angiogenesis assay shows that FGF-2 released from the AlgS-Ph hydrogel promotes the formation of blood vessels. These results indicate that the AlgS-Ph hydrogel is a suitable candidate for the FGF-2 carrier. Full article

(This article belongs to the Special Issue Advanced Gels for Drug Delivery Systems Based on Sustainable Development Goals (SDGs))

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14 pages, 3560 KiB

Open AccessArticle

Polyacrylamide/poly(2-(dimethylamino) Ethyl Methacrylate) Interpenetrating Polymer Networks as Drug Delivery Systems for Diclofenac Sodium

by Kristina Grigorova, Bistra Kostova, Dilyana Georgieva, Anton Apostolov and Elena Vassileva

Gels 2022, 8(12), 780; https://doi.org/10.3390/gels8120780 - 29 Nov 2022

Cited by 1 | Viewed by 1352

Abstract

Nowadays, modern pharmaceutical investigations are directed toward the design and production of drug delivery systems for achieving prolonged and controlled drug delivery. In this respect, the use of interpenetrating polymer networks (IPNs) is an opportunity in the preparation of polymer drug delivery systems [...] Read more.

Nowadays, modern pharmaceutical investigations are directed toward the design and production of drug delivery systems for achieving prolonged and controlled drug delivery. In this respect, the use of interpenetrating polymer networks (IPNs) is an opportunity in the preparation of polymer drug delivery systems with desired characteristics. This paper describes the synthesis and characterization of novel poly(2-(dimethylamino) ethyl methacrylate) (PDMAEMA) and polyacrylamide (PAAm)-based IPNs with different compositions and their application as diclofenac sodium delivery systems. The prepared IPNs were shown to possess phase-separated structures at the nano level, as revealed by SEM and TM-DSC. The IPNs’ composition was shown to determine the swelling behavior of these novel materials, and the inclusion of the charged IPN component (PDMAEMA) has changed the water molecules type diffusion from Fickian to non-Fickian, as revealed by the swelling kinetics study. Loading efficiency of diclofenac sodium and diclofenac sodium content in the polymer network was evaluated, and in vitro drug release experiments were carried out in order to estimate the ability of the obtained IPNs to control the release of the water-soluble drug. Full article

(This article belongs to the Special Issue Advanced Gels for Drug Delivery Systems Based on Sustainable Development Goals (SDGs))

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22 pages, 5831 KiB

Open AccessArticle

pH Responsive Hydrogels for the Delivery of Capecitabine: Development, Optimization and Pharmacokinetic Studies

by Umaira Rehman, Rai Muhammad Sarfraz, Asif Mahmood, Shehla Akbar, Ahmed E. Altyar, Roaa M. Khinkar and Heba A. Gad

Gels 2022, 8(12), 775; https://doi.org/10.3390/gels8120775 - 28 Nov 2022

Cited by 8 | Viewed by 1597

Abstract

The objective of the current study was to achieve a sustained release profile of capecitabine (CAP), an anticancer agent frequently administered in conventional dosage form due to its short plasma half-life. A drug-loaded smart pH responsive chitosan/fenugreek-g-poly (MAA) hydrogel was synthesized by an [...] Read more.

The objective of the current study was to achieve a sustained release profile of capecitabine (CAP), an anticancer agent frequently administered in conventional dosage form due to its short plasma half-life. A drug-loaded smart pH responsive chitosan/fenugreek-g-poly (MAA) hydrogel was synthesized by an aqueous free radical polymerization technique. The developed network was evaluated for capecitabine loading %, swelling response, morphology, structural and compositional characteristics, and drug release behavior. Significantly higher swelling and in vitro drug release rate were exhibited by formulations at pH 7.4 than at pH 1.2, demonstrating the pH responsive character of hydrogels. Swelling percentage and CAP loading ranged within 74.45–83.54% and 50.13–72.43%, respectively. Maximum release, up to 93%, was demonstrated over 30 h, evidencing the controlled release pattern of CAP from hydrogels. The optimized formulation was further screened for acute oral toxicity studies. No signs of oral, dermal, or ocular toxicities were noticed, confirming safety evidence of the network. Furthermore, pharmacokinetic analysis demonstrated the sustained release response of CAP from hydrogels as confirmed by a significant increase in plasma half-life (t_1/2) (13 h) and AUC (42.88 µg h/mL) of CAP. Based on these findings, fabricated hydrogels are strongly recommended as a biocompatible carrier for colorectal delivery of active agents. Full article

(This article belongs to the Special Issue Advanced Gels for Drug Delivery Systems Based on Sustainable Development Goals (SDGs))

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24 pages, 11339 KiB

Open AccessArticle

Nanoemulsion-Based Hydrogels and Organogels Containing Propolis and Dexpanthenol: Preparation, Characterization, and Comparative Evaluation of Stability, Antimicrobial, and Cytotoxic Properties

by Rukiye Sevinç-Özakar, Emrah Seyret, Emrah Özakar and Mehmet Cemal Adıgüzel

Gels 2022, 8(9), 578; https://doi.org/10.3390/gels8090578 - 10 Sep 2022

Cited by 12 | Viewed by 3276

Abstract

Recently, nanoemulsion-based gels have become very popular for dermal drug delivery, overcoming the disadvantages of conventional semi-solid drug forms. The aim of this study is to prepare and characterize nanoemulsion-based hydrogels and organogels containing combined propolis and dexpanthenol, and to compare their stability, [...] Read more.

Recently, nanoemulsion-based gels have become very popular for dermal drug delivery, overcoming the disadvantages of conventional semi-solid drug forms. The aim of this study is to prepare and characterize nanoemulsion-based hydrogels and organogels containing combined propolis and dexpanthenol, and to compare their stability, antimicrobial, and cytotoxicity properties. Within the scope of characterization studies, organoleptic properties, drug content, morphology, pH, gel-sol conversion temperature, spreadability, viscosity, FT-IR, and release properties were evaluated in hydrogels and organogels. The characterization studies carried out were subjected to short-term stability evaluation at room temperature and refrigerator for 3 months. While no phase separation was observed in any of the formulations kept in the refrigerator, phase separation was observed in four formulations kept at room temperature. The release study successfully obtained an extended release for propolis and dexpanthenol. In the antimicrobial susceptibility study, Hydrogel 1 showed activity against S. aureus, while Organogel 1 showed activity against both S. aureus and S. epidermidis. In the cytotoxicity study against HDFa cells, both Hydrogel 1 and Organogel 1 were found to be nontoxic at low doses. These hydrogels and organogels, which contain propolis and dexpanthenol in combination for the first time, are promising systems that can be used in wound and burn models in the future. Full article

(This article belongs to the Special Issue Advanced Gels for Drug Delivery Systems Based on Sustainable Development Goals (SDGs))

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19 pages, 4063 KiB

Open AccessArticle

Imatinib Mesylate-Loaded Rosin/Cinnamon Oil-Based In Situ Forming Gel against Colorectal Cancer Cells

by Ei Mon Khaing, Torsak Intaraphairot, Jongjan Mahadlek, Siriporn Okonogi, Wiwat Pichayakorn and Thawatchai Phaechamud

Gels 2022, 8(9), 526; https://doi.org/10.3390/gels8090526 - 23 Aug 2022

Cited by 6 | Viewed by 1895

Abstract

Localized delivery systems have been typically designed to enhance drug concentration at a target site and minimize systemic drug toxicity. A rosin/cinnamon oil (CO) in situ forming gel (ISG) was developed for the sustainable delivery of imatinib mesylate (IM) against colorectal cancer cells. [...] Read more.

Localized delivery systems have been typically designed to enhance drug concentration at a target site and minimize systemic drug toxicity. A rosin/cinnamon oil (CO) in situ forming gel (ISG) was developed for the sustainable delivery of imatinib mesylate (IM) against colorectal cancer cells. CO has been claimed to express a potent anticancer effect against various cancer cells, as well as a synergistic effect with IM on colorectal cancer cells; however, poor aqueous solubility limits its application. The effect of rosin with the adding CO was assessed on physicochemical properties and in vitro drug release from developed IM-loaded rosin/CO-based ISG. Moreover, in vitro cytotoxicity tests were conducted against two colorectal cancer cells. All formulations exhibited Newtonian flow behavior with viscosity less than 266.9 cP with easier injectability. The adding of CO decreased the hardness and increased the adhesive force of the obtained rosin gel. The gel formation increased over time under microscopic observation. CO-added ISG had a particle-like gel appearance, and it promoted a higher release of IM over a period of 28 days. All tested ISG formulations revealed cytotoxicity against HCT-116 and HT-29 cell lines at different incubation times. Thus, CO-loaded rosin-based ISG can act as a potentially sustainable IM delivery system for chemotherapy against colorectal cancer cells. Full article

(This article belongs to the Special Issue Advanced Gels for Drug Delivery Systems Based on Sustainable Development Goals (SDGs))

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15 pages, 1310 KiB

Open AccessArticle

Increasing the Hydrophobic Component of Poloxamers and the Inclusion of Salt Extend the Release of Bupivacaine from Injectable In Situ Gels, While Common Polymer Additives Have Little Effect

by Hani Abdeltawab, Darren Svirskis, Andrew G. Hill and Manisha Sharma

Gels 2022, 8(8), 484; https://doi.org/10.3390/gels8080484 - 02 Aug 2022

Cited by 2 | Viewed by 1611

Abstract

Various strategies have been applied to reduce the initial burst of drug release and sustain release from poloxamer-based thermoresponsive gels. This work focussed on investigating different formulation approaches to minimise the initial burst of release and sustain the release of the small hydrophilic [...] Read more.

Various strategies have been applied to reduce the initial burst of drug release and sustain release from poloxamer-based thermoresponsive gels. This work focussed on investigating different formulation approaches to minimise the initial burst of release and sustain the release of the small hydrophilic drug bupivacaine hydrochloride from poloxamer-based thermoresponsive gels. Various in situ gel formulations were prepared by varying the polypropylene oxide (PPO)/polyethylene oxide (PEO) ratio and by adding additives previously described in the literature. It was observed that increasing the PPO/PEO ratio from 0.28 to 0.30 reduced the initial burst release from 17.3% ± 1.8 to 9.1% ± 1.2 during the first six hours and extended the release profile from 10 to 14 days. Notably, the inclusion of sodium chloride (NaCl 0.4% w/w) further reduced the initial burst release to 1.8% ± 1.1 over the first 6 h. Meanwhile, physical blending with additive polymers had a negligible effect on the burst release and overall release profile. The findings suggest that extended release of bupivacaine hydrochloride, with reduced initial burst release, can be achieved simply by increasing the PPO/PEO ratio and the inclusion of NaCl. Full article

(This article belongs to the Special Issue Advanced Gels for Drug Delivery Systems Based on Sustainable Development Goals (SDGs))

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11 pages, 1790 KiB

Open AccessFeature PaperArticle

Inhibition of Colon Cancer Recurrence via Exogenous TRAIL Delivery Using Gel-like Coacervate Microdroplets

by Sungjun Kim, Yerim Jwa, Jiyeon Hong and Kyobum Kim

Gels 2022, 8(7), 427; https://doi.org/10.3390/gels8070427 - 08 Jul 2022

Cited by 5 | Viewed by 1589

Abstract

Colon cancer (CC) belongs to the three major malignancies with a high recurrence rate. Therefore, a novel drug delivery system that can prevent CC recurrence while minimizing side effects is needed. Tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL) has recently been spotlighted as a protein drug [...] Read more.

Colon cancer (CC) belongs to the three major malignancies with a high recurrence rate. Therefore, a novel drug delivery system that can prevent CC recurrence while minimizing side effects is needed. Tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL) has recently been spotlighted as a protein drug that can induce apoptosis of cancer cells specifically. However, its short in vivo half-life is still a challenge to overcome. Hence, in this study, a gel-like mPEGylated coacervate (mPEG-Coa) delivery platform was developed through electrostatic interaction of mPEG-poly(ethylene arginylaspartate diglyceride) (mPEG-PEAD) and heparin for effective protection of cargo TRAIL, subsequently preserving its bioactivity. mPEG-Coa could protect cargo TRAIL against protease. Sustained release was observed for a long-term (14 days). In addition, recurrence of HCT-116 cells was suppressed when cells were treated with TRAIL-loaded mPEG-Coa for 7 days through long-term continuous supply of active TRAIL, whereas re-proliferation occurred in the bolus TRAIL-treated group. Taken together, these results suggest that our gel-like mPEG-Coa could be utilized as a functional delivery platform to suppress CC recurrence by exogenously supplying TRAIL for a long time with a single administration. Full article

(This article belongs to the Special Issue Advanced Gels for Drug Delivery Systems Based on Sustainable Development Goals (SDGs))

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24 pages, 3897 KiB

Open AccessArticle

Intranasal Delivery of Darunavir-Loaded Mucoadhesive In Situ Gel: Experimental Design, In Vitro Evaluation, and Pharmacokinetic Studies

by Anroop B. Nair, Sunita Chaudhary, Hiral Shah, Shery Jacob, Vivek Mewada, Pottathil Shinu, Bandar Aldhubiab, Nagaraja Sreeharsha, Katharigatta N. Venugopala, Mahesh Attimarad and Jigar Shah

Gels 2022, 8(6), 342; https://doi.org/10.3390/gels8060342 - 30 May 2022

Cited by 21 | Viewed by 3065

Abstract

The clinical efficacy of antiretroviral therapy in NeuroAIDS is primarily limited by the low perfusion of the drug to the brain. The objective of the current investigation was to design and develop an in situ mucoadhesive gel loaded with darunavir to assess the [...] Read more.

The clinical efficacy of antiretroviral therapy in NeuroAIDS is primarily limited by the low perfusion of the drug to the brain. The objective of the current investigation was to design and develop an in situ mucoadhesive gel loaded with darunavir to assess the feasibility of brain targeting through the intranasal route. Preliminary batches (F1–F9) were prepared and evaluated for various pharmaceutical characteristics. A full factorial design of the experiment was applied to optimize and assess the effect of two influencing variables (Carbopol 934P (X₁) and Poloxamer 407 (X₂)) on the response effects (gelation temperature (Y₁) and % drug release (Y₂) at 8 h). The data demonstrate that both influencing variables affect the response variables significantly (p < 0.05). The optimized formulation (F7) exhibited favorable rheological properties, adequate mucoadhesion, sustained drug release, and greater permeation across the nasal mucosa. An in vitro ciliotoxicity study confirms the nontoxicity of the optimized in situ gel (D7) on the nasal mucosa. An in vivo pharmacokinetic study in rats was performed to assess drug targeting to the brain following the nasal application of the selected in situ gel (D7). Significantly higher (p < 0.0001) C_max (~4-fold) and AUC_0-α (~3.5-fold) values were noticed in the brain after nasal application, as compared to the intravenous route. However, less systemic exposure to darunavir was noticed with nasal therapy, which confirms the low absorption of the drug into the central compartment. Overall, the data here demonstrate that the optimized in situ mucoadhesive nasal gel is effective in targeting darunavir to the brain by the nasal route and could be a viable option for the treatment of NeuroAIDS. Full article

(This article belongs to the Special Issue Advanced Gels for Drug Delivery Systems Based on Sustainable Development Goals (SDGs))

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19 pages, 3011 KiB

Open AccessArticle

Development, Characterization and Optimization of the Anti-Inflammatory Influence of Meloxicam Loaded into a Eucalyptus Oil-Based Nanoemulgel

by Tamer M. Shehata, Hanan M. Elnahas and Heba S. Elsewedy

Gels 2022, 8(5), 262; https://doi.org/10.3390/gels8050262 - 22 Apr 2022

Cited by 14 | Viewed by 3008

Abstract

The purpose of the present study was to explore the influence of a certain natural essential oil, namely eucalyptus oil, as an anti-inflammatory agent in addition to its prospective role in enhancing the action of meloxicam in reducing inflammation. As far as we [...] Read more.

The purpose of the present study was to explore the influence of a certain natural essential oil, namely eucalyptus oil, as an anti-inflammatory agent in addition to its prospective role in enhancing the action of meloxicam in reducing inflammation. As far as we know, this has been the first integration of meloxicam and eucalyptus essential oil into a nanoemulgel formulation intended for topical use. Primarily, eucalyptus oil was utilized in developing a nanoemulsion formulation incorporating meloxicam. A 2² factorial design was constructed using two independent variables (oil concentration and surfactant concentration) with two responses (particle size and % of in vitro release). One optimized formula was selected depending on the desirability function and subjected to a stability study. The optimized nanoemulsion was mixed with HPMC as a gelling agent to produce a meloxicam-loaded nanoemulgel, which was examined for its properties, stability, in vitro release and ex vivo permeation. Eventually, the anti-inflammatory activity was evaluated and compared with a placebo and corresponding gel formulation. The developed nanoemulgel revealed acceptable physical characteristics to be applied topically. Studying of the in vitro release was conducted successfully for 6 h. The ex vivo permeation from the nanoemulgel formulations was prompted, showing an appropriate value of the steady-state transdermal flux (SSTF). As a final point, the anti-inflammatory activity of the developed nanoemulgel revealed a valued anti-inflammatory influence. Additionally, the concurrence of eucalyptus essential oil and meloxicam was assured, and their potential in combating and lowering inflammation was supported. Full article

(This article belongs to the Special Issue Advanced Gels for Drug Delivery Systems Based on Sustainable Development Goals (SDGs))

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13 pages, 1364 KiB

Open AccessArticle

The Basic Study of Liposome in Temperature-Sensitive Gel at Body Temperature for Treatment of Peritoneal Dissemination

by Ikumi Sugiyama, Kaana Ando and Yasuyuki Sadzuka

Gels 2022, 8(5), 252; https://doi.org/10.3390/gels8050252 - 20 Apr 2022

Cited by 3 | Viewed by 1663

Abstract

Peritoneal dissemination is a disease that is difficult to treat surgically because it is widely scattered and proliferates in the abdominal cavity. It is a challenge that even if the drug is administered directly into the abdominal cavity, it rapidly disappears from the [...] Read more.

Peritoneal dissemination is a disease that is difficult to treat surgically because it is widely scattered and proliferates in the abdominal cavity. It is a challenge that even if the drug is administered directly into the abdominal cavity, it rapidly disappears from the abdominal cavity, and the therapeutic effect is not optimal, as expected. In this study, for a liposomal paclitaxel in temperature-sensitive gel that is a suspension before administration and a gel after intraperitoneal administration, the antitumor effect of this formulation was evaluated. Temperature-sensitive gels were prepared using methylcellulose, sodium citrate, and macrogol 4000 and mixed with liposomal paclitaxel. Liposomal paclitaxel containing temperature-sensitive gel in the body was administered into the peritoneal cavity of a mouse model of peritoneal dissemination; the number of cells was significantly reduced compared to a paclitaxel solution of liposomal paclitaxel. These results showed that the liposome in temperature-sensitive gel inhibited cell proliferation in the abdominal cavity. This formulation can be administered easily at room temperature, and it gels and remains in the abdominal cavity for a long period, resulting in a more substantial effect than the existing drug. Full article

(This article belongs to the Special Issue Advanced Gels for Drug Delivery Systems Based on Sustainable Development Goals (SDGs))

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16 pages, 3336 KiB

Open AccessArticle

Development and Optimization of Hyaluronic Acid-Poloxamer In-Situ Gel Loaded with Voriconazole Cubosomes for Enhancement of Activity against Ocular Fungal Infection

by Nabil A. Alhakamy, Khaled M. Hosny, Waleed Y. Rizg, Bayan A. Eshmawi, Moutaz Y. Badr, Awaji Y. Safhi and Samar S. A. Murshid

Gels 2022, 8(4), 241; https://doi.org/10.3390/gels8040241 - 14 Apr 2022

Cited by 10 | Viewed by 2443

Abstract

Fungal eye infections are largely disseminated, especially in developing countries where they may leave over half a million people blind per year. The current study aims to boost the voriconazole antifungal efficiency via loading it as cubosomes (VZ-Cub) into hyaluronic acid and poloxamer-based [...] Read more.

Fungal eye infections are largely disseminated, especially in developing countries where they may leave over half a million people blind per year. The current study aims to boost the voriconazole antifungal efficiency via loading it as cubosomes (VZ-Cub) into hyaluronic acid and poloxamer-based ocular in situ gel. VZ-Cub were fabricated applying Box-Behnken design and employing phytantriol, poloxamer F127, and VZ amounts as independent variables. The produced nano vesicles were evaluated for the dependent variables of particle size (PS), entrapment efficiency (EE%), and transcorneal steady-state flux (Jss) of the VZ, and, the obtained optimal VZ-Cub was loaded into an in situ gel base to enhance its ocular residence time. The in situ gel formulation was tested for its gelation temperature, drug release behavior, transcorneal permeation effects, and antifungal activity. The optimized VZ-Cub consisted of 100 mg of phytantriol, 60 mg of poloxamer F127, and 21 mg of VZ. This formulation led to a minimum PS of 71 nm, an EE% of 66%, Jss value of 6.5 µg/(cm²·min), and stability index of 94 ± 2%. The optimized VZ-Cub-loaded in situ gel released 84% VZ after 12 h and yielded a 4.5-fold increase in drug permeation compared with the VZ aqueous dispersion. The antifungal activity, which was obtained by measuring the fungal growth inhibition zones, revealed that the VZ-Cub-loaded in situ gel formulation had a 3.89-fold increase in antifungal activity compared with the VZ dispersion. In summary, an ocular in situ gel loaded with VZ-Cub could be an effective novel nano-paradigm with enhanced transcorneal permeation and antifungal properties. Full article

(This article belongs to the Special Issue Advanced Gels for Drug Delivery Systems Based on Sustainable Development Goals (SDGs))

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19 pages, 3005 KiB

Open AccessArticle

Design and Comparative Evaluation of Vancomycin HCl-Loaded Rosin-Based In Situ Forming Gel and Microparticles

by Tiraniti Chuenbarn, Jitnapa Sirirak, Sarun Tuntarawongsa, Siriporn Okonogi and Thawatchai Phaechamud

Gels 2022, 8(4), 231; https://doi.org/10.3390/gels8040231 - 08 Apr 2022

Cited by 13 | Viewed by 2461

Abstract

Vancomycin hydrochloride (HCl) is a glycopeptide antibiotic used to treat serious or life-threatening infections, and it reduces plaque scores and gingivitis in periodontal patients. In this study, vancomycin HCl was incorporated into rosin in situ forming gel (ISG) and rosin in situ forming [...] Read more.

Vancomycin hydrochloride (HCl) is a glycopeptide antibiotic used to treat serious or life-threatening infections, and it reduces plaque scores and gingivitis in periodontal patients. In this study, vancomycin HCl was incorporated into rosin in situ forming gel (ISG) and rosin in situ forming microparticles (ISM) to generate a local drug delivery system to treat periodontal disease. The physical properties of the ISG and ISM were measured, including pH, viscosity, injectability, adhesion properties, in-vitro transformation, and drug release. Moreover, the effectiveness of antimicrobial activity was tested using the agar-cup diffusion method against Staphylococcus aureus, Streptococcus mutans, Porphyromonas gingivalis, and Escherichia coli. Vancomycin HCl-loaded rosin-based ISG and ISM had a pH value in the range of 5.02–6.48 and exhibited the ease of injection with an injection force of less than 20 N. Additionally, the lubricity effect of the external oil phase of ISM promoted less work of injection than ISG and 40–60% rosin-based ISM showed good emulsion stability. The droplet size of emulsions containing 40%, 50%, and 60% rosin was 98.48 ± 16.11, 125.55 ± 4.75, and 137.80 ± 16.8 µm, respectively. Their obtained microparticles were significantly smaller in diameter, 78.63 ± 12.97, 93.81 ± 10.53, and 118.32 ± 15.61 µm, respectively, because the particles shrank due to the solvent loss from solvent exchange. Moreover, increasing the concentration of rosin increased the size of microparticles. After phase transformation, all formulations had better plasticity properties than elasticity; therefore, they could easily adapt to the specific shape of a patient’s gum cavity. Both developed ISG and ISM presented inhibition zones against S. mutans and P. gingivalis, with ISG presenting significantly more effectively against these two microbes (p < 0.05). The vancomycin HCl-loaded rosin ISG and ISM delayed drug release for 7 days with efficient antimicrobial activities; thus, they exhibit potential as the drug delivery systems for periodontitis treatment. Full article

(This article belongs to the Special Issue Advanced Gels for Drug Delivery Systems Based on Sustainable Development Goals (SDGs))

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16 pages, 2004 KiB

Open AccessArticle

Preference, Perception, and Acceptability of Fluid Gels as a Potential Age-Appropriate Dosage Form for Elderly Patients with Dysphagia

by Zul Hadif Abd Aziz, Haliza Katas, Marhanis Salihah Omar, Noraida Mohamed Shah, Salma Mohamad Yusop, Mohamad Nasir Shafiee and Siti Fatimah Mohd Tarmizi

Gels 2022, 8(4), 218; https://doi.org/10.3390/gels8040218 - 01 Apr 2022

Cited by 2 | Viewed by 2607

Abstract

The development of pharmaceutical dosage forms that are tailored to specific populations according to their preferences and acceptability could improve medication adherence, which could lead to effective pharmacotherapy. This study evaluated the preference for and perceptions of fluid gels as a potential age-appropriate [...] Read more.

The development of pharmaceutical dosage forms that are tailored to specific populations according to their preferences and acceptability could improve medication adherence, which could lead to effective pharmacotherapy. This study evaluated the preference for and perceptions of fluid gels as a potential age-appropriate dosage form for older adults with dysphagia. The palatability and swallowability of the developed fluid gels were also assessed to determine the consumer acceptability of this formulation. A cross-sectional survey was conducted through the electronic distribution of a self-administered questionnaire among adults in Malaysia between April and December 2021. A randomized and double-blinded clinical study was conducted to evaluate the palatability and swallowability of the fluid gels in 30 healthy participants. A cross-sectional study involving 673 respondents revealed that the fluid gels were perceived positively by consumers (64.4%), were easily swallowed (50.8%), were safe to be consumed (45.3%), and were suitable as a new pharmaceutical formulation (43.8%). The clinical study shows that moderately thickened fluid gels masked the bitterness of the medication and were easily swallowed. The newly developed fluid gels were also positively perceived by the participants. Taken together, fluid gels have shown great potential as an innovative oral formulation that is suitable for consumption by elderly patients with dysphagia. Full article

(This article belongs to the Special Issue Advanced Gels for Drug Delivery Systems Based on Sustainable Development Goals (SDGs))

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Review

Jump to: Research

17 pages, 2723 KiB

Open AccessReview

Targeted Cancer Therapy via pH-Functionalized Nanoparticles: A Scoping Review of Methods and Outcomes

by Stefan Morarasu, Bianca Codrina Morarasu, Razvan Ghiarasim, Adina Coroaba, Crina Tiron, Radu Iliescu and Gabriel-Mihail Dimofte

Gels 2022, 8(4), 232; https://doi.org/10.3390/gels8040232 - 11 Apr 2022

Cited by 8 | Viewed by 2441

Abstract

(1) Background: In recent years, several studies have described various and heterogenous methods to sensitize nanoparticles (NPs) to pH changes; therefore, in this current scoping review, we aimed to map current protocols for pH functionalization of NPs and analyze the outcomes of drug-loaded [...] Read more.

(1) Background: In recent years, several studies have described various and heterogenous methods to sensitize nanoparticles (NPs) to pH changes; therefore, in this current scoping review, we aimed to map current protocols for pH functionalization of NPs and analyze the outcomes of drug-loaded pH-functionalized NPs (pH-NPs) when delivered in vivo in tumoral tissue. (2) Methods: A systematic search of the PubMed database was performed for all published studies relating to in vivo models of anti-tumor drug delivery via pH-responsive NPs. Data on the type of NPs, the pH sensitization method, the in vivo model, the tumor cell line, the type and name of drug for targeted therapy, the type of in vivo imaging, and the method of delivery and outcomes were extracted in a separate database. (3) Results: One hundred and twenty eligible manuscripts were included. Interestingly, 45.8% of studies (n = 55) used polymers to construct nanoparticles, while others used other types, i.e., mesoporous silica (n = 15), metal (n = 8), lipids (n = 12), etc. The mean acidic pH value used in the current literature is 5.7. When exposed to in vitro acidic environment, without exception, pH-NPs released drugs inversely proportional to the pH value. pH-NPs showed an increase in tumor regression compared to controls, suggesting better targeted drug release. (4) Conclusions: pH-NPs were shown to improve drug delivery and enhance antitumoral effects in various experimental malignant cell lines. Full article

(This article belongs to the Special Issue Advanced Gels for Drug Delivery Systems Based on Sustainable Development Goals (SDGs))

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