Research

16 pages, 9235 KiB

Open AccessArticle

Hyaluronic Acid-Based Injective Medical Devices: In Vitro Characterization of Novel Formulations Containing Biofermentative Unsulfated Chondroitin or Extractive Sulfated One with Cyclodextrins

by Valentina Vassallo, Celeste Di Meo, Giuseppe Toro, Alberto Alfano, Giovanni Iolascon and Chiara Schiraldi

Pharmaceuticals 2023, 16(10), 1429; https://doi.org/10.3390/ph16101429 - 09 Oct 2023

Cited by 2 | Viewed by 932 | Correction

Abstract

Currently, chondroitin sulfate (CS) and hyaluronic acid (HA) pharma-grade forms are used for osteoarthritis (OA) management, CS as an oral formulations component, and HA as intra-articular injective medical devices. Recently, unsulfated chondroitin, obtained through biofermentative (BC) manufacturing, has been proposed for thermally stabilized [...] Read more.

Currently, chondroitin sulfate (CS) and hyaluronic acid (HA) pharma-grade forms are used for osteoarthritis (OA) management, CS as an oral formulations component, and HA as intra-articular injective medical devices. Recently, unsulfated chondroitin, obtained through biofermentative (BC) manufacturing, has been proposed for thermally stabilized injective preparation with HA. This study aimed to highlight the specific properties of two commercial injective medical devices, one based on HA/BC complexes and the other containing HA, extractive CS, and cyclodextrins, in order to provide valuable information for joint disease treatments. Their biophysical and biomechanical features were assayed; in addition, biological tests were performed on human pathological chondrocytes. Rheological measurements displayed similar behavior, with a slightly higher G′ for HA/BC, which also proved superior stability to the hyaluronidase attack. Both samples reduced the expression of specific OA-related biomarkers such as NF-kB, interleukin 6 (IL-6), and metalloprotease-13 (MMP-13). Moreover, HA/BC better ensured chondrocyte phenotype maintenance by up-regulating collagen type 2A1 (COLII) and aggrecan (AGN). Notwithstanding, the similarity of biomolecule components, the manufacturing process, raw materials characteristics, and specific concentration resulted in affecting the biomechanical and, more interestingly, the biochemical properties, suggesting potential better performances of HA/BC in joint disease treatment. Full article

(This article belongs to the Special Issue Hydrogels for Pharmaceutical and Biomedical Applications)

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19 pages, 5929 KiB

Open AccessArticle

Injectable Thermosensitive Hyaluronic Acid Hydrogels for Chondrocyte Delivery in Cartilage Tissue Engineering

by Chih-Hao Chen, Hao-Hsi Kao, Yen-Chen Lee and Jyh-Ping Chen

Pharmaceuticals 2023, 16(9), 1293; https://doi.org/10.3390/ph16091293 - 13 Sep 2023

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Abstract

In this study, we synthesize a hyaluronic acid-g-poly(N-isopropylacrylamide) (HPN) copolymer by grafting the amine-terminated poly(N-isopropylacrylamide) (PNIPAM-NH₂) to hyaluronic acid (HA). The 5% PNIPAM-NH₂ and HPN polymer solution is responsive to temperature changes with sol-to-gel phase transition temperatures around [...] Read more.

In this study, we synthesize a hyaluronic acid-g-poly(N-isopropylacrylamide) (HPN) copolymer by grafting the amine-terminated poly(N-isopropylacrylamide) (PNIPAM-NH₂) to hyaluronic acid (HA). The 5% PNIPAM-NH₂ and HPN polymer solution is responsive to temperature changes with sol-to-gel phase transition temperatures around 32 °C. Compared with the PNIPAM-NH₂ hydrogel, the HPN hydrogel shows higher water content and mechanical strength, as well as lower volume contraction, making it a better choice as a scaffold for chondrocyte delivery. From an in vitro cell culture, we see that cells can proliferate in an HPN hydrogel with full retention of cell viability and show the phenotypic morphology of chondrocytes. In the HPN hydrogel, chondrocytes demonstrate a differentiated phenotype with the upregulated expression of cartilage-specific genes and the enhanced secretion of extracellular matrix components, when compared with the monolayer culture on tissue culture polystyrene. In vivo studies confirm the ectopic cartilage formation when HPN was used as a cell delivery vehicle after implanting chondrocyte/HPN in nude mice subcutaneously, which is shown from a histological and gene expression analysis. Taken together, the HPN thermosensitive hydrogel will be a promising injectable scaffold with which to deliver chondrocytes in cartilage-tissue-engineering applications. Full article

(This article belongs to the Special Issue Hydrogels for Pharmaceutical and Biomedical Applications)

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22 pages, 4454 KiB

Open AccessArticle

Gellan Gum/Alginate Microparticles as Drug Delivery Vehicles: DOE Production Optimization and Drug Delivery

by Henrique Carrêlo, Maria Teresa Cidade, João Paulo Borges and Paula Soares

Pharmaceuticals 2023, 16(7), 1029; https://doi.org/10.3390/ph16071029 - 19 Jul 2023

Cited by 4 | Viewed by 1018

Abstract

Gellan gum is a biocompatible and easily accessible polysaccharide with excellent properties to produce microparticles as drug delivery systems. However, the production methods often fail in reproducibility, compromising the translational potential of such systems. In this work, the production of gellan gum-based microparticles [...] Read more.

Gellan gum is a biocompatible and easily accessible polysaccharide with excellent properties to produce microparticles as drug delivery systems. However, the production methods often fail in reproducibility, compromising the translational potential of such systems. In this work, the production of gellan gum-based microparticles was optimized using the coaxial air flow method, and an inexpensive and reproducible production method. A design of experiments was used to identify the main parameters that affect microparticle production and optimization, focusing on diameter and dispersibility. Airflow was the most significant factor for both parameters. Pump flow affected the diameter, while the gellan gum/alginate ratio affected dispersibility. Microparticles were revealed to be sensitive to pH with swelling, degradation, and encapsulation efficiency affected by pH. Using methylene blue as a model drug, higher encapsulation, and swelling indexes were obtained at pH 7.4, while a more pronounced release occurred at pH 6.5. Within PBs solutions, the microparticles endured up to two months. The microparticle release profiles were studied using well-known models, showing a Fickian-type release, but with no alteration by pH. The developed microparticles showed promising results as drug-delivery vehicles sensitive to pH. Full article

(This article belongs to the Special Issue Hydrogels for Pharmaceutical and Biomedical Applications)

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23 pages, 8018 KiB

Open AccessArticle

Novel Hydrogel Membranes Based on the Bacterial Polysaccharide FucoPol: Design, Characterization and Biological Properties

by Diana Araújo, Matilde Martins, Patrícia Concórdio-Reis, Catarina Roma-Rodrigues, Maria Morais, Vítor D. Alves, Alexandra R. Fernandes and Filomena Freitas

Pharmaceuticals 2023, 16(7), 991; https://doi.org/10.3390/ph16070991 - 11 Jul 2023

Cited by 3 | Viewed by 1490

Abstract

FucoPol, a fucose-rich polyanionic polysaccharide, was used for the first time for the preparation of hydrogel membranes (HMs) using Fe³⁺ as a crosslinking agent. This study evaluated the impact of Fe³⁺ and FucoPol concentrations on the HMs’ strength. The results show [...] Read more.

FucoPol, a fucose-rich polyanionic polysaccharide, was used for the first time for the preparation of hydrogel membranes (HMs) using Fe³⁺ as a crosslinking agent. This study evaluated the impact of Fe³⁺ and FucoPol concentrations on the HMs’ strength. The results show that, above 1.5 g/L, Fe³⁺ concentration had a limited influence on the HMs’ strength, and varying the FucoPol concentration had a more significant effect. Three different FucoPol concentrations (1.0, 1.75 and 2.5 wt.%) were combined with Fe³⁺ (1.5 g/L), resulting in HMs with a water content above 97 wt.% and an Fe³⁺ content up to 0.16 wt.%. HMs with lower FucoPol content exhibited a denser porous microstructure as the polymer concentration increased. Moreover, the low polymer content HM presented the highest swelling ratio (22.3 ± 1.8 g/g) and a lower hardness value (32.4 ± 5.8 kPa). However, improved mechanical properties (221.9 ± 10.2 kPa) along with a decrease in the swelling ratio (11.9 ± 1.6 g/g) were obtained for HMs with a higher polymer content. Furthermore, all HMs were non-cytotoxic and revealed anti-inflammatory activity. The incorporation of FucoPol as a structuring agent and bioactive ingredient in the development of HMs opens up new possibilities for its use in tissue engineering, drug delivery and wound care management. Full article

(This article belongs to the Special Issue Hydrogels for Pharmaceutical and Biomedical Applications)

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19 pages, 2890 KiB

Open AccessArticle

Stability Profile and Clinical Evaluation of an Innovative Hydrogel Containing Polymeric Micelles as Drug Delivery Systems with Oregano Essential Oil against Fibroepithelial Polyps

by Larisa Bora, Andrada Iftode, Ana Maria Muț, Lavinia Lia Vlaia, Gheorghe-Emilian Olteanu, Delia Muntean, Cristina Adriana Dehelean, Valentina Buda, Georgeta Hermina Coneac and Corina Danciu

Pharmaceuticals 2023, 16(7), 980; https://doi.org/10.3390/ph16070980 - 08 Jul 2023

Viewed by 1231

Abstract

Skin tags, also known as fibroepithelial polyps (FPs) or acrochordons, are soft, pigmented excrescences, with a prevalence of 50–60% in the population, occurring especially in the fourth decade of life. To date, FPs have been efficiently eliminated using minimum invasive methods such as [...] Read more.

Skin tags, also known as fibroepithelial polyps (FPs) or acrochordons, are soft, pigmented excrescences, with a prevalence of 50–60% in the population, occurring especially in the fourth decade of life. To date, FPs have been efficiently eliminated using minimum invasive methods such as surgical removal, cauterization, laser irradiation, and cryosurgery. Over-the-counter treatments are also of interest for patients due to their non-invasive character, but their clinical efficiency has not been clearly demonstrated. This study was designed in order to evaluate the efficacy of a modern-pharmaceutical-formulation-type poloxamer-based binary hydrogel, having Origanum vulgare L. essential oil (OEO-PbH) as an active ingredient in the management of FPs. The formulation has been shown to possess good qualities in terms of stability and sterility. Non-invasive measurements revealed changes in some physiological skin parameters. An increase in transepidermal water loss (TEWL) and erythema index was noted, while skin surface water content (SWC) decreased during eight weeks of treatment. The macroscopic evaluation revealed that the FPs dried and shrunk after topical treatment with OEO-PbH. Clinically, patients presented a lowering of the number of lesions on the treated area of 20–30% after one month of treatment and around 50% after the second month. Histopathological examination suggests that topical treatment with OEO-PbH may induce histological changes in the epidermis, dermis, and fibrovascular cores of FPs, including a loss of thickness, reduced size and number of blood vessels, and low cellularity. These changes may contribute to the observed reduction in size of FPs after treatment with OEO-PbH. Full article

(This article belongs to the Special Issue Hydrogels for Pharmaceutical and Biomedical Applications)

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15 pages, 3377 KiB

Open AccessArticle

Enhancement of Scaffold In Vivo Biodegradability for Bone Regeneration Using P28 Peptide Formulations

by Farah Alwani Azaman, Margaret E. Brennan Fournet, Suzina Sheikh Ab Hamid, Muhamad Syahrul Fitri Zawawi, Valdemiro Amaro da Silva Junior and Declan M. Devine

Pharmaceuticals 2023, 16(6), 876; https://doi.org/10.3390/ph16060876 - 13 Jun 2023

Cited by 1 | Viewed by 1207

Abstract

The field of bone tissue engineering has shown a great variety of bone graft substitute materials under development to date, with the aim to reconstruct new bone tissue while maintaining characteristics close to the native bone. Currently, insufficient scaffold degradation remains the critical [...] Read more.

The field of bone tissue engineering has shown a great variety of bone graft substitute materials under development to date, with the aim to reconstruct new bone tissue while maintaining characteristics close to the native bone. Currently, insufficient scaffold degradation remains the critical limitation for the success of tailoring the bone formation turnover rate. This study examines novel scaffold formulations to improve the degradation rate in vivo, utilising chitosan (CS), hydroxyapatite (HAp) and fluorapatite (FAp) at different ratios. Previously, the P28 peptide was reported to present similar, if not better performance in new bone production to its native protein, bone morphogenetic protein-2 (BMP-2), in promoting osteogenesis in vivo. Therefore, various P28 concentrations were incorporated into the CS/HAp/FAp scaffolds for implantation in vivo. H&E staining shows minimal scaffold traces in most of the defects induced after eight weeks, showing the enhanced biodegradability of the scaffolds in vivo. The HE stain highlighted the thickened periosteum indicating a new bone formation in the scaffolds, where CS/HAp/FAp/P28 75 µg and CS/HAp/FAp/P28 150 µg showed the cortical and trabecular thickening. CS/HAp/FAp 1:1 P28 150 µg scaffolds showed a higher intensity of calcein green label with the absence of xylenol orange label, which indicates that mineralisation and remodelling was not ongoing four days prior to sacrifice. Conversely, double labelling was observed in the CS/HAp/FAp 1:1 P28 25 µg and CS/HAp/FAp/P28 75 µg, which indicates continued mineralisation at days ten and four prior to sacrifice. Based on the HE and fluorochrome label, CS/HAp/FAp 1:1 with P28 peptides presented a consistent positive osteoinduction following the implantation in the femoral condyle defects. These results show the ability of this tailored formulation to improve the scaffold degradation for bone regeneration and present a cost-effective alternative to BMP-2. Full article

(This article belongs to the Special Issue Hydrogels for Pharmaceutical and Biomedical Applications)

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14 pages, 5777 KiB

Open AccessArticle

Reduction-Responsive Chitosan-Based Injectable Hydrogels for Enhanced Anticancer Therapy

by Trung Thang Vu, Sonyabapu Yadav, Obireddy Sreekanth Reddy, Sung-Han Jo, Soo-Bin Joo, Byeong Kook Kim, Eun Ju Park, Sang-Hyug Park and Kwon Taek Lim

Pharmaceuticals 2023, 16(6), 841; https://doi.org/10.3390/ph16060841 - 05 Jun 2023

Cited by 2 | Viewed by 1622

Abstract

Selective delivery of anticancer drug molecules to the tumor site enhances local drug dosages, which leads to the death of cancer cells while simultaneously minimizing the negative effects of chemotherapy on other tissues, thereby improving the patient’s quality of life. To address this [...] Read more.

Selective delivery of anticancer drug molecules to the tumor site enhances local drug dosages, which leads to the death of cancer cells while simultaneously minimizing the negative effects of chemotherapy on other tissues, thereby improving the patient’s quality of life. To address this need, we developed reduction-responsive chitosan-based injectable hydrogels via the inverse electron demand Diels–Alder reaction between tetrazine groups of disulfide-based cross-linkers and norbornene groups of chitosan derivatives, which were applied to the controlled delivery of doxorubicin (DOX). The swelling ratio, gelation time (90–500 s), mechanical strength (G’~350–850 Pa), network morphology, and drug-loading efficiency (≥92%) of developed hydrogels were investigated. The in vitro release studies of the DOX-loaded hydrogels were performed at pH 7.4 and 5.0 with and without DTT (10 mM). The biocompatibility of pure hydrogel and the in vitro anticancer activity of DOX-loaded hydrogels were demonstrated via MTT assay on HEK-293 and HT-29 cancer cell lines, respectively. Full article

(This article belongs to the Special Issue Hydrogels for Pharmaceutical and Biomedical Applications)

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23 pages, 8141 KiB

Open AccessArticle

Design and Optimization of Omeprazole-Curcumin-Loaded Hydrogel Beads Coated with Chitosan for Treating Peptic Ulcers

by Eman J. Heikal, Rashad M. Kaoud, Shadeed Gad, Hatem I. Mokhtar, Afaf A. Aldahish, Wafa Ali Alzlaiq, Sawsan A. Zaitone, Yasser M. Moustafa and Taha M. Hammady

Pharmaceuticals 2023, 16(6), 795; https://doi.org/10.3390/ph16060795 - 27 May 2023

Cited by 4 | Viewed by 1737

Abstract

This study aimed to formulate a pharmaceutical dosage form containing omeprazole (OMP) and curcumin (CURC) to treat experimental peptic ulcers. OMP and CURC were preliminarily complexed with hydroxypropyl-β-cyclodextrin for enhancing their solubilization. After that, the combined complex (CURC/OMP) was loaded to alginate beads [...] Read more.

This study aimed to formulate a pharmaceutical dosage form containing omeprazole (OMP) and curcumin (CURC) to treat experimental peptic ulcers. OMP and CURC were preliminarily complexed with hydroxypropyl-β-cyclodextrin for enhancing their solubilization. After that, the combined complex (CURC/OMP) was loaded to alginate beads to sustain their release and then coated with chitosan. Finally, we tested the anti-ulcerogenic impact of the best formula versus free OMP or OMP-only-loaded beads. The formulated spherical beads’ diameter ranged from a minimum value of 1.5 ± 0.08 mm to 2.6 ± 0.24 mm; the swelling results ranged from 400.00 ± 8.5% to 800.00 ± 6.2%. The entrapment efficiency was in a range from 60.85 ± 1.01% to 87.44 ± 1.88%. The optimized formula (F8) showed a maximum EE% (87.44 ± 1.88%), swelling (800.00 ± 6.2%), and diameter in the range of 2.60 ± 0.24, with a desirability of 0.941. In the first hour following the administration of the free drug complex, 95% of OMP and 98% of CURC were released. This is unacceptable for medications that require a delayed release in the stomach. The initial drug release from hydrogel beads was 23.19% for CURC and 17.19% for OMP after 2 h and 73.09% for CURC and 58.26% for OMP after 12 h; however, after 24 h, 87.81% of CURC and 81.67% of OMP had been released. The OMP/CURC beads showed a more stable particle size (0.52 ± 0.01 mm) after 6 weeks. In conclusion, the OMP/CURC hydrogel beads give stronger anti-ulcer effectiveness compared to free OMP, CURC-only beads, and OMP-only-loaded beads, indicating a prospective application for managing peptic ulcers. Full article

(This article belongs to the Special Issue Hydrogels for Pharmaceutical and Biomedical Applications)

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25 pages, 6804 KiB

Open AccessArticle

Development and Optimization of Tamarind Gum-β-Cyclodextrin-g-Poly(Methacrylate) pH-Responsive Hydrogels for Sustained Delivery of Acyclovir

by Kanza Shafiq, Asif Mahmood, Mounir M. Salem-Bekhit, Rai Muhammad Sarfraz, Alanood S. Algarni, Ehab I. Taha, Ahd A. Mansour, Sami Al Zahrani and Yacine Benguerba

Pharmaceuticals 2022, 15(12), 1527; https://doi.org/10.3390/ph15121527 - 08 Dec 2022

Cited by 5 | Viewed by 1777

Abstract

Acyclovir has a short half-life and offers poor bioavailability. Its daily dose is 200 mg five times a day. A tamarind gum and β-cyclodextrin-based pH-responsive hydrogel network for sustained delivery of acyclovir was developed using the free-radical polymerization technique. Developed networks were characterized [...] Read more.

Acyclovir has a short half-life and offers poor bioavailability. Its daily dose is 200 mg five times a day. A tamarind gum and β-cyclodextrin-based pH-responsive hydrogel network for sustained delivery of acyclovir was developed using the free-radical polymerization technique. Developed networks were characterized by FTIR, DSC, TGA, PXRD, EDX, and SEM. The effect of varying feed ratios of polymers, monomers, and crosslinker on the gel fraction, swelling, and release was also investigated. FTIR findings confirmed the compatibility of the ingredients in a new complex polymer. The thermal stability of acyclovir was increased within the newly synthesized polymer. SEM photomicrographs confirmed the porous texture of hydrogels. The gel fraction was improved (from 90.12% to 98.12%) with increased reactant concentrations. The pH of the dissolution medium and the reactant contents affected swelling dynamics and acyclovir release from the developed carrier system. Based on the R2 value, the best-fit model was zero-order kinetics with non-Fickian diffusion as a release mechanism. The biocompatibility of the developed network was confirmed through hematology, LFT, RFT, lipid profile, and histopathological examinations. No sign of pathology, necrosis, or abrasion was observed. Thus, a pH-responsive and biocompatible polymeric system was developed for sustained delivery of acyclovir to reduce the dosing frequency and improve patient compliance. Full article

(This article belongs to the Special Issue Hydrogels for Pharmaceutical and Biomedical Applications)

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17 pages, 4664 KiB

Open AccessArticle

Engineered-Skin of Single Dermal Layer Containing Printed Hybrid Gelatin-Polyvinyl Alcohol Bioink via 3D-Bioprinting: In Vitro Assessment under Submerged vs. Air-Lifting Models

by Syafira Masri, Faraheda Amilia Mohd Fauzi, Sarah Batrisyia Hasnizam, Aizzaty Sulha Azhari, Juliana Edora Amin Lim, Looi Qi Hao, Manira Maarof, Antonella Motta and Mh Busra Fauzi

Pharmaceuticals 2022, 15(11), 1328; https://doi.org/10.3390/ph15111328 - 27 Oct 2022

Cited by 3 | Viewed by 1981

Abstract

Three-dimensional (3D) in vitro skin models are frequently employed in cosmetic and pharmaceutical research to minimize the demand for animal testing. Hence, three-dimensional (3D) bioprinting was introduced to fabricate layer-by-layer bioink made up of cells and improve the ability to develop a rapid [...] Read more.

Three-dimensional (3D) in vitro skin models are frequently employed in cosmetic and pharmaceutical research to minimize the demand for animal testing. Hence, three-dimensional (3D) bioprinting was introduced to fabricate layer-by-layer bioink made up of cells and improve the ability to develop a rapid manufacturing process, while maintaining bio-mechanical scaffolds and microstructural properties. Briefly, gelatin-polyvinyl alcohol (GPVA) was mixed with 1.5 × 10⁶ and 3.0 × 10⁶ human dermal fibroblast (HDF) cell density, together with 0.1% genipin (GNP), as a crosslinking agent, using 3D-bioprinting. Then, it was cultured under submerged and air-lifting conditions. The gross appearance of the hydrogel’s surface and cross-section were captured and evaluated. The biocompatibility testing of HDFs and cell–bioink interaction towards the GPVA was analyzed by using live/dead assay, cell migration activity, cell proliferation assay, cell morphology (SEM) and protein expression via immunocytochemistry. The crosslinked hydrogels significantly demonstrated optimum average pore size (100–199 μm). The GPVA crosslinked with GNP (GPVA_GNP) hydrogels with 3.0 × 10⁶ HDFs was proven to be outstanding, compared to the other hydrogels, in biocompatibility testing to promote cellular interaction. Moreover, GPVA–GNP hydrogels, encapsulated with 3.0 × 10⁶ HDFs under submerged cultivation, had a better outcome than air-lifting with an excellent surface cell viability rate of 96 ± 0.02%, demonstrated by 91.3 ± 4.1% positively expressed Ki67 marker at day 14 that represented active proliferative cells, an average of 503.3 ± 15.2 μm for migration distance, and maintained the HDFs’ phenotypic profiles with the presence of collagen type I expression. It also presented with an absence of alpha-smooth muscle actin positive staining. In conclusion, 3.0 × 10⁶ of hybrid GPVA hydrogel crosslinked with GNP, produced by submerged cultivation, was proven to have the excellent biocompatibility properties required to be a potential bioinks for the rapid manufacturing of 3D in vitro of a single dermal layer for future use in cosmetic, pharmaceutic and toxicologic applications. Full article

(This article belongs to the Special Issue Hydrogels for Pharmaceutical and Biomedical Applications)

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28 pages, 5153 KiB

Open AccessArticle

Novel Bile Salt Stabilized Vesicles-Mediated Effective Topical Delivery of Diclofenac Sodium: A New Therapeutic Approach for Pain and Inflammation

by Tamer M. Mahmoud, Mohamed M. Nafady, Hanan O. Farouk, Dina M. Mahmoud, Yasmin M. Ahmed, Randa Mohammed Zaki and Doaa S. Hamad

Pharmaceuticals 2022, 15(9), 1106; https://doi.org/10.3390/ph15091106 - 05 Sep 2022

Cited by 14 | Viewed by 2286

Abstract

The oral delivery of diclofenac sodium (DNa), a non-steroidal analgesic, anti-inflammatory drug, is associated with various gastrointestinal side effects. The aim of the research was to appraise the potential of transdermal delivery of DNa using bilosomes as a vesicular carrier (BSVC) in inflamed [...] Read more.

The oral delivery of diclofenac sodium (DNa), a non-steroidal analgesic, anti-inflammatory drug, is associated with various gastrointestinal side effects. The aim of the research was to appraise the potential of transdermal delivery of DNa using bilosomes as a vesicular carrier (BSVC) in inflamed paw edema. DNa-BSVCs were elaborated using a thin-film hydration technique and optimized using a 3¹.2² multilevel categoric design with Design Expert^® software 10 software (Stat-Ease, Inc., Minneapolis, MI, USA). The effect of formulation variables on the physicochemical properties of BSVC, as well as the optimal formulation selection, was investigated. The BSVCs were evaluated for various parameters including entrapment efficiency (EE%), vesicle size (VS), zeta potential (ZP) and permeation studies. The optimized BSVC was characterized for in vitro release, Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM) and incorporated into hydrogel base. The optimized DNa-BSVC gel effectiveness was assessed in vivo using carrageenan-induced paw edema animal model via cyclooxygenase 2 (COX-2), interleukin 6 (IL-6), Hemooxygenase 1 (HO-1) and nuclear factor-erythroid factor2-related factor 2 (Nfr-2) that potentiate anti-inflammatory and anti-oxidant activity coupled with histopathological investigation. The resulting vesicles presented VS from 120.4 ± 0.65 to 780.4 ± 0.99 nm, EE% from 61.7 ± 3.44 to 93.2 ± 2.21%, ZP from −23.8 ± 2.65 to −82.1 ± 12.63 mV and permeation from 582.9 ± 32.14 to 1350.2 ± 45.41 µg/cm². The optimized BSVCs were nano-scaled spherical vesicles with non-overlapped bands of their constituents in the FTIR. Optimized formulation has superior skin permeability ex vivo approximately 2.5 times greater than DNa solution. Furthermore, histological investigation discovered that the formed BSVC had no skin irritating properties. It was found that DNa-BSVC gel suppressed changes in oxidative inflammatory mediators (COX-2), IL-6 and consequently enhanced Nrf2 and HO-1 levels. Moreover, reduction of percent of paw edema by about three-folds confirmed histopathological alterations. The results revealed that the optimized DNa-BSVC could be a promising transdermal drug delivery system to boost anti-inflammatory efficacy of DNa by enhancing the skin permeation of DNa and suppressing the inflammation of rat paw edema. Full article

(This article belongs to the Special Issue Hydrogels for Pharmaceutical and Biomedical Applications)

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21 pages, 4524 KiB

Open AccessArticle

Enhanced In Vivo Wound Healing Efficacy of a Novel Hydrogel Loaded with Copper (II) Schiff Base Quinoline Complex (CuSQ) Solid Lipid Nanoparticles

by Doaa Abou El-ezz, Laila H. Abdel-Rahman, Badriah Saad Al-Farhan, Dalia A. Mostafa, Eman G. Ayad, Maram T. Basha, Mahmoud Abdelaziz and Ehab M. Abdalla

Pharmaceuticals 2022, 15(8), 978; https://doi.org/10.3390/ph15080978 - 08 Aug 2022

Cited by 20 | Viewed by 3137

Abstract

Wound dressings created using nanotechnology are known as suitable substrates to speed up the healing of both acute and chronic wounds. Therapeutic substances can be delivered using these materials. In this study, a hydrogel loaded with Cu (II) Schiff base 8-hydroxy quinoline complex [...] Read more.

Wound dressings created using nanotechnology are known as suitable substrates to speed up the healing of both acute and chronic wounds. Therapeutic substances can be delivered using these materials. In this study, a hydrogel loaded with Cu (II) Schiff base 8-hydroxy quinoline complex (CuSQ) solid lipid nanoparticles (SLN) was formulated to investigate its wound healing potential in an excision wound healing model in rats. The CuSQ SLN were spherical shaped with sizes ranging from 111 to 202 nm and a polydispersity index (PDI) ranging from 0.43 to 0.76, encapsulation efficiency (EE) % between 85 and 88, and zeta potential (ZP) of −11.8 to −40 mV. The formulated hydrogel showed good homogeneity, good stability, and a pH of 6.4 which indicates no skin irritation and had no cytotoxicity on the human skin fibroblast (HSF) cell line. In the in vivo study, animals were placed in five groups: control, standard, plain hydrogel, low dose, and high dose of CuSQ hydrogel. Both doses of CuSQ showed significantly faster healing rates compared to standard and control rats. In addition, the histopathology study showed more collagen, improved angiogenesis, and intact re-epithelization with less inflammation. A significant increase in transforming growth factor-beta1 (TGF-β1) level and increased immune expression of vascular endothelial growth factor (VEGF) by CuSQ treatment validates its role in collagen synthesis, proliferation of fibroblasts and enhancement of angiogenesis. Matrix metalloproteinase-9 (MMP-9) was found to be significantly reduced after CuSQ treatment. Immunohistochemistry of tumor necrosis factor alpha (TNF-α) revealed a marked decrease in inflammation. Thus, we concluded that CuSQ would be a beneficial drug for cutaneous wound healing since it effectively accelerated wound healing through regulation of various cytokines and growth factors. Full article

(This article belongs to the Special Issue Hydrogels for Pharmaceutical and Biomedical Applications)

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20 pages, 2564 KiB

Open AccessArticle

Nano-Silica Carriers Coated by Chloramphenicol: Synthesis, Characterization, and Grinding Trial as a Way to Improve the Release Profile

by Radosław Balwierz, Dawid Bursy, Paweł Biernat, Nataliia Hudz, Mariia Shanaida, Łukasz Krzemiński, Paweł Skóra, Monika Biernat and Wioletta Ochędzan Siodłak

Pharmaceuticals 2022, 15(6), 703; https://doi.org/10.3390/ph15060703 - 02 Jun 2022

Cited by 2 | Viewed by 2748

Abstract

Silica nanoparticles were applied as the carrier of chloramphenicol (2,2-dichloro-N-[(1R,2R)-1,3-dihydroxy-1-(4-nitrophenyl)propan-2-yl]acetamide), and were loaded in a 1% carbopol-based gel (poly(acrylic acid)), which allowed obtainment of an upgraded drug form. The samples of silica materials were obtained by means [...] Read more.

Silica nanoparticles were applied as the carrier of chloramphenicol (2,2-dichloro-N-[(1R,2R)-1,3-dihydroxy-1-(4-nitrophenyl)propan-2-yl]acetamide), and were loaded in a 1% carbopol-based gel (poly(acrylic acid)), which allowed obtainment of an upgraded drug form. The samples of silica materials were obtained by means of modified Stöber synthesis, and their morphological properties were analyzed using Fourier transform infrared spectroscopy (FTIR), Brunauer–Emmett–Teller (BET) method, elemental analysis (EA), thermogravimetric analysis (TGA), analysis of the specific surface properties, X-ray diffraction study (XRD), scanning electron microscope (SEM), and dynamic light scattering (DLS) methods, which permitted the selection of the drug carrier. The two obtained silica carriers were coated with chloramphenicol and loaded into 1% carbopol gel. The release studies were then performed. The release results were evaluated using mathematical models as well as model-independent analysis. It was found that the modification of the synthesis of the silica by the sol-gel method to form a product coated with chloramphenicol and further grinding of the silica material influenced the release of the active substance, thus allowing the modification of its pharmaceutical availability. The change in the parameters of silica synthesis influenced the structure and morphological properties of the obtained silica carrier. The grinding process determined the way of adsorption of the active substance on its surface. The studies showed that the proper choice of silica carrier has a considerable effect on the release profile of the prepared hydrogel formulations. Full article

(This article belongs to the Special Issue Hydrogels for Pharmaceutical and Biomedical Applications)

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New Challenges and Prospective Applications of Three-Dimensional Bioactive Polymeric Hydrogels in Oral and Craniofacial Tissue Engineering: A Narrative Review

by Gamal Abdel Nasser Atia, Hany K. Shalaby, Naema Goda Ali, Shaimaa Mohammed Morsy, Mohamed Mohamady Ghobashy, Hager Abdel Nasser Attia, Paritosh Barai, Norhan Nady, Ahmad S. Kodous and Hasi Rani Barai

Pharmaceuticals 2023, 16(5), 702; https://doi.org/10.3390/ph16050702 - 05 May 2023

Cited by 7 | Viewed by 1861

Abstract

Regenerative medicine, and dentistry offers enormous potential for enhancing treatment results and has been fueled by bioengineering breakthroughs over the previous few decades. Bioengineered tissues and constructing functional structures capable of healing, maintaining, and regenerating damaged tissues and organs have had a broad [...] Read more.

Regenerative medicine, and dentistry offers enormous potential for enhancing treatment results and has been fueled by bioengineering breakthroughs over the previous few decades. Bioengineered tissues and constructing functional structures capable of healing, maintaining, and regenerating damaged tissues and organs have had a broad influence on medicine and dentistry. Approaches for combining bioinspired materials, cells, and therapeutic chemicals are critical in stimulating tissue regeneration or as medicinal systems. Because of its capacity to maintain an unique 3D form, offer physical stability for the cells in produced tissues, and replicate the native tissues, hydrogels have been utilized as one of the most frequent tissue engineering scaffolds during the last twenty years. Hydrogels’ high water content can provide an excellent conditions for cell viability as well as an architecture that mimics real tissues, bone, and cartilage. Hydrogels have been used to enable cell immobilization and growth factor application. This paper summarizes the features, structure, synthesis and production methods, uses, new challenges, and future prospects of bioactive polymeric hydrogels in dental and osseous tissue engineering of clinical, exploring, systematical and scientific applications. Full article

(This article belongs to the Special Issue Hydrogels for Pharmaceutical and Biomedical Applications)

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