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A special issue of Gels (ISSN 2310-2861). This special issue belongs to the section "Gel Applications".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 15877

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Dr. Mireia Mallandrich Miret

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Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain
Interests: nanocarriers; topical drug delivery systems; dermal absorption; skin models; in vitro studies; nanomedicine; transdermal delivery; transmucosal delivery; cronocosmetic; skin biodistribution
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Dr. Francisco Fernández-Campos

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R&D Department, Labiana Pharmaceuticals, 08757 Corbera Llobregat, Barcelona, Spain
Interests: nanotechnology; molecular mechanism of anti-inflammatory drugs; antibiotics and antifungals; drug delivery systems; topical inflammatory diseases; pharmacokinetics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Gels and Nanogels are promising drug delivery systems for different administration routes (oral, parenteral, or topical) due to their biocompatibility and biodegradability, which allow for them to modify biological properties and the pharmacokinetic profile. Advances in polymer sciences and polymer structural modifications give nanogels interesting properties, such as their responsiveness to different stimuli (pH, temperature, ionic strength, endogenous compounds, etc.), improved adhesion to biological surfaces, and improved anti-microbiological properties, among others. In addition, advances in gel manufacturing processes could improve the efficiency of the drug delivery system, potentially promoting a more realistic approach for real patient administration.

We propose this Special Issue, “Recent Advances on Gels Engineering for Drug Delivery”, to contribute the latest information about the potential use of gels and nanogels to treat different diseases and to explore novel approaches, including new manufacturing and composition properties focusing on biomedical applications. Research and review manuscripts are welcome.

Dr. Mireia Mallandrich
Dr. Francisco Fernández-Campos
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Gels is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

gels and nanogels
drug delivery
biomedical applications
topical administration
oral administration
parenteral administration
stimuli-responsive gels

Related Special Issue

Recent Advances in Gels Engineering for Drug Delivery (2nd Edition) in Gels

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Research

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16 pages, 4999 KiB

Open AccessArticle

Synthesis and Characterization of Alginate Gel Beads with Embedded Zeolite Structures as Carriers of Hydrophobic Curcumin

by Gianluca Ciarleglio, Federica Cinti, Elisa Toto and Maria Gabriella Santonicola

Gels 2023, 9(9), 714; https://doi.org/10.3390/gels9090714 - 03 Sep 2023

Cited by 5 | Viewed by 1642

Abstract

Alginate-based beads containing a porous zeolite filler were developed as carriers of bioactive compounds with a hydrophobic nature, such as curcumin (Cur). Curcumin, a natural pigment extracted from the turmeric (Curcuma longa) plant, exhibits antioxidant, anti-inflammatory, anticarcinogenic, and antiviral properties. To enhance the bioavailability of the drug, curcumin needs to be encapsulated in a suitable carrier that improves its dispersibility and solubility. Commercial A-type zeolites (Z5A) were used as curcumin-binding agents and they were immobilized within the alginate gel beads by cross-linking in calcium chloride solution during an extrusion dripping process. The process parameters (alginate and CaCl₂ concentrations, needle gauge, collecting distance) were optimized to fabricate beads with good sphericity factor and 1.5–1.7 mm diameter in their hydrated state. The chemical structure of the gel beads was assessed using FTIR spectroscopy, while their thermal stability was evaluated through differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Due to the alginate matrix, the composite Alg/ZA5-Cur beads possess pH-responsive properties. In addition, the gel beads were modified by chitosan (CS) to enhance the stability and control the degradation behavior of the gel matrix. The swelling behavior and the degradation of the beads were analyzed in physiological solutions with different pH values. Results demonstrate the stabilizing and protective effect of the chitosan coating, as well as the reinforcing effect of the zeolite filler. This makes the pH-responsive alginate gel beads good candidates for the delivery of lipophilic drugs to specific inflammatory sites. Full article

(This article belongs to the Special Issue Recent Advances in Gels Engineering for Drug Delivery)

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19 pages, 3818 KiB

Open AccessArticle

Development of Soft Luliconazole Invasomes Gel for Effective Transdermal Delivery: Optimization to In-Vivo Antifungal Activity

by Sunitha Kumari, Omar Awad Alsaidan, Dibyalochan Mohanty, Ameeduzzafar Zafar, Swagatika Das, Jeetendra Kumar Gupta and Mohammad Khalid

Gels 2023, 9(8), 626; https://doi.org/10.3390/gels9080626 - 03 Aug 2023

Cited by 1 | Viewed by 1462

Abstract

Luliconazole (LZ) is a good candidate for the treatment of fungal infection topically but has limitations, i.e., poor solubility and poor permeability to skin. Due to these limitations, multiple administrations for a long time are required to treat the inflection. The aim of the present study was to develop the invasomes (IVS) gel of LZ to improve the topical antifungal activity. The IVS was prepared by the thin-film hydration method and optimized by Box-Bhekhen design software. The optimized LZIVS (LZIVSopt) has 139.1 ± 4.32 nm of vesicle size, 88.21 ± 0.82% of entrapment efficiency, 0.301 ± 0.012 of PDI, and 19.5 mV (negative) of zeta potential. Scanning microscopy showed a spherical shape of the vesicle. FTIR spectra showed there is no interaction between the drug and lipid. Thermogram showed that the LZ is encapsulated into the LZIVS matrix. LZIVSopt gel (LZIVSopt-G3) exhibited optimum viscosity (6493 ± 27 cps) and significant spreadability (7.2 g·cm/s). LZIVSopt-G3 showed 2.47-fold higher permeation than pure LZ-gel. LZIVSopt-G3 did not show any edema or swelling in the skin, revealing that the developed formulation is non-irritant. LZIVSopt-G3 exhibited significant inhibition of the fungus infection (C. albicans) in the infected rats. The finding concluded that IVS gel is a good carrier and an attractive approach for the enhancement of topical delivery of LZ to treat the fungal infection. Full article

(This article belongs to the Special Issue Recent Advances in Gels Engineering for Drug Delivery)

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15 pages, 4218 KiB

Open AccessArticle

The Preparation and Characterization of N,N-Dimethyl Acrylamide-Diallyl Maleate Gel/Hydrogel in a Non-Aqueous Solution

by Md Murshed Bhuyan, Mobinul Islam and Jae-Ho Jeong

Gels 2023, 9(8), 598; https://doi.org/10.3390/gels9080598 - 25 Jul 2023

Cited by 1 | Viewed by 1178

Abstract

A few drugs need non-aqueous gels for release in the specific region of the intestine. The present work focuses on preparing N,N-Dimethyl acrylamide-Diallyl Maleate (DMAA-DAM) gel in Dimethyl sulfoxide (DMSO) solvent by applying different doses of gamma radiation and then characterization. The blend solution of 10%: 10%—DMAA: DAM was prepared in DMSO and irradiated at 2, 5, 10, 20, and 30 kGy doses from the Co-60 gamma source. After extraction, it was observed that all of the radiation doses yielded more than 95% gel content. The best gel content was found for 10 kGy dose, which was 97%. The equilibrium swelling was optimized 1800% of the dried gel for 5 kGy dose. Gel formation was confirmed by analyzing characteristic functional groups and the environment of protons in the gel structure by using FTIR and NMR spectroscopy. The thermal stability was tested using DSC and TGA which showed the glass transition temperature at 86.55 °C and the degradation started at 320 °C. The XRD pattern analysis revealed the semi-crystalline nature of the gel. Therefore, DMAA-DAM gels can be a good candidate for use in different fields of study, especially in drug delivery. Full article

(This article belongs to the Special Issue Recent Advances in Gels Engineering for Drug Delivery)

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13 pages, 3756 KiB

Open AccessEditor’s ChoiceArticle

Dual pH- and Thermo-Sensitive Poly(N-isopropylacrylamide-co-allylamine) Nanogels for Curcumin Delivery: Swelling–Deswelling Behavior and Phase Transition Mechanism

by Madhappan Santhamoorthy and Seong-Cheol Kim

Gels 2023, 9(7), 536; https://doi.org/10.3390/gels9070536 - 01 Jul 2023

Cited by 1 | Viewed by 1604

Abstract

Curcumin (Cur) is a beneficial ingredient with numerous bioactivities. However, due to its low solubility and poor bioavailability, its therapeutic application is limited. In this work, we prepared poly-N-isopropylacrylamide p(NIPAm) and polyallylamine p(Am)-based nanogel (p(NIPAm-co-Am)) NG for a dual pH- and temperature-sensitive copolymer system for drug delivery application. In this copolymer system, the p(NIPAm) segment was incorporated to introduce thermoresponsive behavior and the p(Am) segment was incorporated to introduce drug binding sites (amine groups) in the resulting (p(NIPAm-co-Am)) NG system. Various instrumental characterizations including ¹H nuclear magnetic resonance (¹H NMR) spectroscopy, Fourier transform infrared (FT-IR) analysis, scanning electron microscopy (SEM), zeta potential, and particle size analysis were performed to confirm the copolymer synthesis. Curcumin (Cur), an anticancer bioactive substance, was employed to assess the in vitro drug loading and release performance of the resulting copolymer nanogels system at varied pH levels (pH 7.2, 6.5, and 4.0) and temperatures (25 °C, 37 °C, and 42 °C). The cytocompatibility of the p(NIPAm-co-Am) NG sample was also tested on MDA-MB-231 cells at various sample concentrations. All the study results indicate that the p(NIPAm-co-Am) NG produced might be effective for drug loading and release under pH and temperature dual-stimuli conditions. As a result, the p(NIPAm-co-Am) NG system has the potential to be beneficial in the use of drug delivery applications in cancer therapy. Full article

(This article belongs to the Special Issue Recent Advances in Gels Engineering for Drug Delivery)

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24 pages, 5282 KiB

Open AccessArticle

Aloe vera-Based Polymeric Network: A Promising Approach for Sustained Drug Delivery, Development, Characterization, and In Vitro Evaluation

by Arshad Mahmood, Alia Erum, Ume Ruqia Tulain, Sharmeen Shafiq, Nadia Shamshad Malik, Sidra, Muhammad Tariq Khan and Mohammed S. Alqahtani

Gels 2023, 9(6), 474; https://doi.org/10.3390/gels9060474 - 08 Jun 2023

Cited by 2 | Viewed by 1601

Abstract

The present study was conducted to fabricate and characterize mucilage-based polymeric networks of Aloe vera for controlled drug release. Aloe vera mucilage was used to develop a polymeric network via the free-radical polymerization method using potassium persulphate as the initiator, N′ N′-Methylene bisacrylamide as the crosslinker, and acrylamide as the monomer. Using varying concentrations of Aloe vera mucilage, crosslinker, and monomer, we developed different formulations. Swelling studies were conducted at pH 1.2 and 7.4. Concentrations of polymer, monomer, and crosslinker were optimized as a function of swelling. Porosity and gel content were calculated for all samples. FTIR, SEM, XRD, TGA, and DSC studies were conducted for the characterization of polymeric networks. Thiocolchicoside was used as a model drug to study the in vitro release in acidic and alkaline pH. Various kinetics models were applied by using a DD solver. Increasing content of monomer and crosslinker swelling, porosity, and drug release decreased while gel content increased. An increase in Aloe vera mucilage concentration promotes swelling, porosity, and drug release of the polymeric network but decreases gel content. The FTIR study confirmed the formation of crosslinked networks. SEM indicated that the polymeric network had a porous structure. DSC and XRD studies indicated the entrapment of drugs inside the polymeric networks in amorphous form. The analytical method was validated according to ICH guidelines in terms of linearity, range, LOD, LOQ, accuracy, precision, and robustness. Analysis of drug release mechanism revealed Fickian behavior of all formulations. All these results indicated that the M1 formulation was considered to be the best polymeric network formulation in terms of sustaining drug release patterns. Full article

(This article belongs to the Special Issue Recent Advances in Gels Engineering for Drug Delivery)

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18 pages, 14138 KiB

Open AccessArticle

Experimental Correction and Treatment of Chronic Liver Failure Using Implantable Cell-Engineering Constructs of the Auxiliary Liver Based on a Bioactive Heterogeneous Biopolymer Hydrogel

by Murat Shagidulin, Nina Onishchenko, Victor Sevastianov, Mikhail Krasheninnikov, Aleksey Lyundup, Alla Nikolskaya, Alena Kryzhanovskaya, Sofia Voznesenskaia, Mariia Gorelova, Nadezhda Perova, Igor Kozlov, Artem Venediktov, Gennadii Piavchenko and Sergey Gautier

Gels 2023, 9(6), 456; https://doi.org/10.3390/gels9060456 - 01 Jun 2023

Cited by 1 | Viewed by 1089

Abstract

Our study sought approaches for chronic liver failure (CLF) treatment and correction via cell-engineered constructs (CECs). They are built from biopolymer-based, microstructured, and collagen-containing hydrogel (BMCG). We also strove to evaluate the functional activity of BMCG in liver regeneration. Materials and Methods: Allogeneic liver cells (namely, hepatocytes; LC) together with mesenchymal multipotent stem cells of bone marrow origin (MMSC BM; BMSCs) were adhered to our BMCG to compose implanted liver CECs. Thereafter, we investigated a model of CLF in rats receiving the implanted CECs. The CLF had been provoked by long-term exposure to carbon tetrachloride. The study comprised male Wistar rats (n = 120) randomized into 3 groups: Group 1 was a control group with the saline treatment of the hepatic parenchyma (n = 40); Group 2 received BMCG only (n = 40); and Group 3 was loaded with CECs implanted into the parenchyma of their livers (n = 40). August rats (n = 30) made up a donor population for LCs and MMSC BM to develop grafts for animals from Group 3. The study length was 90 days. Results: CECs were shown to affect both biochemical test values and morphological parameters in rats with CLF. Conclusion: We found BMCG-derived CECs to be operational and active, with regenerative potential. Group 3 showed significant evidence of forced liver regeneration that tended to persist until the end of the study (day 90). The phenomenon is reflected by biochemical signs of hepatic functional recovery by day 30 after grafting (compared to Groups 1 and 2), whereas structural features of liver repair (necrosis prevention, missing formation of vacuoles, degenerating LC number decrease, and delay of hepatic fibrotic transformation). Such implantation of BMCG-derived CECs with allogeneic LCs and MMSC BM might represent a proper option to correct and treat CLF, as well as to maintain affected liver function in patients with liver grafting needed. Full article

(This article belongs to the Special Issue Recent Advances in Gels Engineering for Drug Delivery)

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14 pages, 2316 KiB

Open AccessArticle

Incorporation of Resveratrol in Polymeric Nanogel for Improvement of Its Protective Effects on Cellular and Microsomal Oxidative Stress Models

by Lyubomira Radeva, Denitsa Stefanova, Yordan Yordanov, Katya Kamenova, Petar D. Petrov, Maya K. Marinova, Svilen P. Simeonov, Magdalena Kondeva-Burdina, Virginia Tzankova and Krassimira Yoncheva

Gels 2023, 9(6), 450; https://doi.org/10.3390/gels9060450 - 30 May 2023

Cited by 1 | Viewed by 1402

Abstract

Nanogels are attractive drug delivery systems that provide high loading capacity for drug molecules, improve their stability, and increase cellular uptake. Natural antioxidants, especially polyphenols such as resveratrol, are distinguished by low aqueous solubility, which hinders therapeutic activity. Thus, in the present study, resveratrol was incorporated into nanogel particles, aiming to improve its protective effects in vitro. The nanogel was prepared from natural substances via esterification of citric acid and pentane-1,2,5-triol. High encapsulation efficiency (94.5%) was achieved by applying the solvent evaporation method. Dynamic light scattering, atomic force microscopy, and transmission electron microscopy revealed that the resveratrol-loaded nanogel particles were spherical in shape with nanoscopic dimensions (220 nm). In vitro release tests showed that a complete release of resveratrol was achieved for 24 h, whereas at the same time the non-encapsulated drug was poorly dissolved. The protective effect of the encapsulated resveratrol against oxidative stress in fibroblast and neuroblastoma cells was significantly stronger compared to the non-encapsulated drug. Similarly, the protection in a model of iron/ascorbic acid-induced lipid peroxidation on rat liver and brain microsomes was higher with the encapsulated resveratrol. In conclusion, embedding resveratrol in this newly developed nanogel improved its biopharmaceutical properties and protective effects in oxidative stress models. Full article

(This article belongs to the Special Issue Recent Advances in Gels Engineering for Drug Delivery)

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22 pages, 5851 KiB

Open AccessArticle

Caspofungin-Loaded Formulations for Treating Ocular Infections Caused by Candida spp.

by Noelia Pérez-González, María J. Rodríguez-Lagunas, Ana C. Calpena-Campmany, Nuria Bozal-de Febrer, Lyda Halbaut-Bellowa, Mireia Mallandrich and Beatriz Clares-Naveros

Gels 2023, 9(4), 348; https://doi.org/10.3390/gels9040348 - 20 Apr 2023

Cited by 1 | Viewed by 1483

Abstract

Fungal keratitis causes corneal blindness worldwide. The treatment includes antibiotics, with Natamycin being the most commonly used; however, fungal keratitis is difficult to treat, so alternative therapies are needed. In situ gelling formulations are a promising alternative; this type of formulation has the advantages of eye drops combined with the advantages of ointments. This study was designed to develop and characterize three formulations containing 0.5% CSP: CSP-O1, CSP-O2, and CSP-O3. CSP is an antifungal drug that acts against a diverse variety of fungi, and Poloxamer 407 (P407) is a polymer of synthetic origin that is able to produce biocompatible, biodegradable, highly permeable gels and is known to be thermoreversible. Short-term stability showed that formulations are best stored at 4 °C, and rheological analysis showed that the only formulation able to gel in situ was CSP-O3. In vitro release studies indicated that CSP-O1 releases CSP most rapidly, while in vitro permeation studies showed that CSP-O3 permeated the most. The ocular tolerance study showed that none of the formulations caused eye irritation. However, CSP-O1 decreased the cornea’s transparency. Histological results indicate that the formulations are suitable for use, with the exception of CSP-O3, which induced slight structural changes in the scleral structure. All formulations were shown to have antifungal activity. In view of the results obtained, these formulations could be promising candidates for use in the treatment of fungal keratitis. Full article

(This article belongs to the Special Issue Recent Advances in Gels Engineering for Drug Delivery)

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23 pages, 23298 KiB

Open AccessArticle

Synergistic Antimicrobial Activity of Magnetite and Vancomycin-Loaded Mesoporous Silica Embedded in Alginate Films

by Georgiana Dolete, Cornelia-Ioana Ilie, Cristina Chircov, Bogdan Purcăreanu, Ludmila Motelica, Alina Moroșan, Ovidiu Cristian Oprea, Denisa Ficai, Ecaterina Andronescu and Lia-Mara Dițu

Gels 2023, 9(4), 295; https://doi.org/10.3390/gels9040295 - 02 Apr 2023

Viewed by 1307

Abstract

The aim of the present study was to obtain a hydrogel-based film as a carrier for the sustained and controlled release of vancomycin, an antibiotic commonly used in various types of infections. Considering the high-water solubility of vancomycin (>50 mg/mL) and the aqueous medium underlying the exudates, a prolonged release of vancomycin from an MCM-41 carrier was sought. The present work focused on the synthesis of malic acid coated magnetite (Fe₃O₄/malic) by co-precipitation, synthesis of MCM-41 by a sol-gel method and loading of MCM-41 with vancomycin, and their use in alginate films for wound dressing. The nanoparticles obtained were physically mixed and embedded in the alginate gel. Prior to incorporation, the nanoparticles were characterized by XRD, FT-IR and FT-Raman spectroscopy, TGA-DSC and DLS. The films were prepared by a simple casting method and were further cross-linked and examined for possible heterogeneities by means of FT-IR microscopy and SEM. The degree of swelling and the water vapor transmission rate were determined, considering their potential use as wound dressings. The obtained films show morpho-structural homogeneity, sustained release over 48 h and a strong synergistic enhancement of the antimicrobial activity as a consequence of the hybrid nature of these films. The antimicrobial efficacy was tested against S. aureus, two strains of E. faecalis (including vancomycin-resistant Enterococcus, VRE) and C. albicans. The incorporation of magnetite was also considered as an external triggering component in case the films were used as a magneto-responsive smart dressing to stimulate vancomycin diffusion. Full article

(This article belongs to the Special Issue Recent Advances in Gels Engineering for Drug Delivery)

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23 pages, 945 KiB

Open AccessEditor’s ChoiceReview

Current Advances in Stimuli-Responsive Hydrogels as Smart Drug Delivery Carriers

by Yulong Zhang and Benjamin M. Wu

Gels 2023, 9(10), 838; https://doi.org/10.3390/gels9100838 - 22 Oct 2023

Cited by 3 | Viewed by 2355

Abstract

In recent years, significant advancements in the field of advanced materials and hydrogel engineering have enabled the design and fabrication of smart hydrogels and nanogels that exhibit sensitivity to specific signals or pathological conditions, leading to a wide range of applications in drug delivery and disease treatment. This comprehensive review aims to provide an in-depth analysis of the stimuli-responsive principles exhibited by smart hydrogels in response to various triggers, such as pH levels, temperature fluctuations, light exposure, redox conditions, or the presence of specific biomolecules. The functionality and performance characteristics of these hydrogels are highly influenced by both their constituent components and fabrication processes. Key design principles, their applications in disease treatments, challenges, and future prospects were also discussed. Overall, this review aims to contribute to the current understanding of gel-based drug delivery systems and stimulate further research in this rapidly evolving field. Full article

(This article belongs to the Special Issue Recent Advances in Gels Engineering for Drug Delivery)

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