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Gels
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Advanced Hydrogels for Controlled Drug Delivery
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Advanced Hydrogels for Controlled Drug Delivery

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

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 21643

Special Issue Editor

Prof. Dr. Akira Matsumoto

E-Mail Website
Guest Editor
Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo 101-0062, Japan
Interests: polymer gel; gel; boronic acids; drug delivery systems; biosensors; microneedles
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

I am inviting you to contribute to a Special Issue of Gels entitled “Advanced Hydrogels for Controlled Drug Delivery”.

Gels remain at the forefront of soft matter science and engineering research. Due to their rich diversity of chain–solvent combinations, gels provide ever-growing options for exploring basic and applied chemistry, materials science, food science, pharmaceutical science and medicine. As open systems capable of exchanging energy and substances with their surroundings, gels have long served as a research platform for chemo-mechanical systems and drug delivery applications. Recent findings in vaccine immunology highlight the importance of “dose scheduling”, i.e., the spatiotemporal control of immune stimulators on a day-to-week timescale synchronized with autologous immune kinetics. The same method can be applied in cell engineering and regenerative medicine, challenging experts around the globe to develop advanced hydrogel technologies with this aim in mind.

Dr. Akira Matsumoto
Guest Editor

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 2100 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

  • smart gels
  • nanogels
  • drug delivery
  • cell and tissue engineering
  • injectable gels
  • 3D printing
  • microneedles

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Published Papers (7 papers)

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Research

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19 pages, 8470 KiB  
Article
Solid Lipid Nanoparticles Embedded Hydrogels as a Promising Carrier for Retarding Irritation of Leflunomide
by Hawra Mohammed Alhelal, Sidharth Mehta, Varsha Kadian, Vandita Kakkar, Himanshi Tanwar, Rekha Rao, Bandar Aldhubiab, Nagaraja Sreeharsha, Pottathil Shinu and Anroop B. Nair
Gels 2023, 9(7), 576; https://doi.org/10.3390/gels9070576 - 14 Jul 2023
Cited by 8 | Viewed by 2432
Abstract
Leflunomide (LEF), a disease-modifying anti-rheumatic drug, has been widely explored for its anti-inflammatory potential in skin disorders such as psoriasis and melanoma. However, its poor stability and skin irritation pose challenges for topical delivery. To surmount these issues, LEF-loaded solid lipid nanoparticles (SLNs) [...] Read more.
Leflunomide (LEF), a disease-modifying anti-rheumatic drug, has been widely explored for its anti-inflammatory potential in skin disorders such as psoriasis and melanoma. However, its poor stability and skin irritation pose challenges for topical delivery. To surmount these issues, LEF-loaded solid lipid nanoparticles (SLNs) integrated with hydrogels have been developed in the present investigation. SLNs developed by microemulsion techniques were found ellipsoidal with 273.1 nm particle size and −0.15 mV zeta potential. Entrapment and total drug content of LEF-SLNs were obtained as 65.25 ± 0.95% and 93.12 ± 1.72%, respectively. FTIR and XRD validated the successful fabrication of LEF-SLNs. The higher stability of LEF-SLNs (p < 0.001) compared to pure drug solution was observed in photostability studies. Additionally, in vitro anti-inflammatory activity of LEF-SLNs showed good potential in comparison to pure drugs. Further, prepared LEF-SLNs loaded hydrogel showed ideal rheology, texture, occlusion, and spreadability for topical drug delivery. In vitro release from LEF-SLN hydrogel was found to follow the Korsmeyer-Peppas model. To assess the skin safety of fabricated lipidic formulation, irritation potential was performed employing the HET-CAM technique. In conclusion, the findings of this investigation demonstrated that LEF-SLN hydrogel is capable of enhancing the photostability of the entrapped drug while reducing its skin irritation with improved topical delivery characteristics. Full article
(This article belongs to the Special Issue Advanced Hydrogels for Controlled Drug Delivery)
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26 pages, 11256 KiB  
Article
Development of Novel pH-Sensitive Eudragit Coated Beads Containing Curcumin-Mesalamine Combination for Colon-Specific Drug Delivery
by Eman J. Heikal, Rashad M. Kaoud, Shadeed Gad, Hatem I. Mokhtar, Abdullah Alattar, Reem Alshaman, Sawsan A. Zaitone, Yasser M. Moustafa and Taha M. Hammady
Gels 2023, 9(4), 264; https://doi.org/10.3390/gels9040264 - 23 Mar 2023
Cited by 9 | Viewed by 4972
Abstract
This research aims to develop a drug delivery system that effectively treats colitis while administering curcumin/mesalamine by coating alginate/chitosan beads with Eudragit® S-100 to target the colon. Beads were tested to determine their physicochemical characteristics. Coating with Eudragit® S-100 prevents drug release at [...] Read more.
This research aims to develop a drug delivery system that effectively treats colitis while administering curcumin/mesalamine by coating alginate/chitosan beads with Eudragit® S-100 to target the colon. Beads were tested to determine their physicochemical characteristics. Coating with Eudragit® S-100 prevents drug release at a pH of less than 7; this was demonstrated by in-vitro release conducted in a medium with gradually varying pH to mimic circumstances in various regions of the gastrointestinal tract. This study examined the efficacy of the coated beads in treating acetic acid-induced colitis in rats. Results showed that spherical beads were formed with an average diameter of 1.6–2.8 mm, and the obtained swelling ranged from 409.80% to 890.19%. The calculated entrapment efficiency ranged from 87.49% to 97.89%. The optimized formula F13 (which was composed of mesalamine-curcumin active ingredients, Sodium alginate as a gelling agent, chitosan as a controlled release agent, CaCl2 as a crosslinking agent, and Eudragit S-100 as a pH-sensitive coating agent) demonstrated the best entrapment efficiency (97.89% ± 1.66), swelling (890.19% ± 60.1), and bead size (2.7 ± 0.62 mm). In formulation #13, which was coated with Eudragit S 100, curcumin (6.01 ± 0.04%) and mesalamine (8.64 ± 0.7%), were released after 2 h at pH 1.2; 6.36 ± 0.11% and 10.45 ± 1.52% of curcumin and mesalamine, respectively, were then released after 4 h and at pH 6.8. Meanwhile, at pH 7.4, after 24 h, approximately 85.34 ± 2.3% (curcumin) and 91.5 ± 1.2% (mesalamine) were released. Formula #13 significantly reduced the colitis, and this suggests that the developed hydrogel beads can be used for delivering curcumin-mesalamine combinations to treat ulcerative colitis after adequate research. Full article
(This article belongs to the Special Issue Advanced Hydrogels for Controlled Drug Delivery)
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10 pages, 2021 KiB  
Article
Decoupling between Translational Diffusion and Viscoelasticity in Transient Networks with Controlled Network Connectivity
by Takuya Katashima, Ryunosuke Kobayashi, Shohei Ishikawa, Mitsuru Naito, Kanjiro Miyata, Ung-il Chung and Takamasa Sakai
Gels 2022, 8(12), 830; https://doi.org/10.3390/gels8120830 - 16 Dec 2022
Cited by 4 | Viewed by 1839
Abstract
The mobility of sustained molecules is influenced by viscoelasticity, which is strongly correlated with the diffusional property in polymeric liquid. However, the study of transient networks formed by a reversible crosslink, which is the viscoelastic liquid, was insufficient due to the absence of [...] Read more.
The mobility of sustained molecules is influenced by viscoelasticity, which is strongly correlated with the diffusional property in polymeric liquid. However, the study of transient networks formed by a reversible crosslink, which is the viscoelastic liquid, was insufficient due to the absence of a model system. We compare the viscoelastic and diffusional properties of the transient networks, using the model system with controlled network connectivity (Tetra-PEG slime). According to independent measurements of viscoelasticity and diffusion, the root-mean-square distance the polymer diffuses during the viscoelastic relaxation time shows a large deviation from the self-size of the polymer, which is contrary to the conventional understanding. This decoupling between viscoelasticity and diffusion is unique for transient networks, suggesting that the viscoelastic relaxation is not induced by the diffusion of one prepolymer, particularly in the network with low connectivity. These findings will provide a definite basis for discussion to understand the viscoelasticity in transient networks. Full article
(This article belongs to the Special Issue Advanced Hydrogels for Controlled Drug Delivery)
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15 pages, 3465 KiB  
Article
Bioadhesive Perivascular Microparticle-Gel Drug Delivery System for Intimal Hyperplasia Prevention: In Vitro Evaluation and Preliminary Biocompatibility Assessment
by Tamara Melnik, Alexandre Porcello, François Saucy, Florence Delie and Olivier Jordan
Gels 2022, 8(12), 776; https://doi.org/10.3390/gels8120776 - 28 Nov 2022
Cited by 3 | Viewed by 1953
Abstract
Intimal hyperplasia (IH) is an undesirable pathology occurring after peripheral or coronary bypass surgery. It involves the proliferation and migration of vascular smooth muscle cells, leading to a reduction in the diameter of the vascular lumen, which can lead to stenosis and graft [...] Read more.
Intimal hyperplasia (IH) is an undesirable pathology occurring after peripheral or coronary bypass surgery. It involves the proliferation and migration of vascular smooth muscle cells, leading to a reduction in the diameter of the vascular lumen, which can lead to stenosis and graft failure. Topically applied atorvastatin (ATV) has been shown to slow down this process. To be effective, the drug delivery system should remain at the perivascular site for 5–8 weeks, corresponding to the progression of IH, and be capable of releasing an initial dose of the drug followed by a sustained release. Ideally, bioadhesion would anchor the gel to the application site. To meet these needs, we encapsulated ATV in a 2-component system: a hyaluronic acid–dopamine bioadhesive gel for rapid release and biodegradable microparticles for sustained release. The system was characterized by scanning electron microscopy, rheology, bioadhesion on porcine arteries, and a release profile. The rheological properties were adequate for perivascular application, and we demonstrated superior bioadhesion and cohesion compared to the control HA formulations. The release profile showed a burst, generated by free ATV, followed by sustained release over 8 weeks. A preliminary evaluation of subcutaneous biocompatibility in rats showed good tolerance of the gel. These results offer new perspectives on the perivascular application towards an effective solution for the prevention of IH. Full article
(This article belongs to the Special Issue Advanced Hydrogels for Controlled Drug Delivery)
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13 pages, 13773 KiB  
Article
Synthesis and Characterization of Chitosan-Decorated Nanoemulsion Gel of 5-Fluorouracil for Topical Delivery
by Asif Nawaz, Muhammad Shahid Latif, Maha Abdallah Alnuwaiser, Shafi Ullah, Muhammad Iqbal, Mulham Alfatama and Vuanghao Lim
Gels 2022, 8(7), 412; https://doi.org/10.3390/gels8070412 - 30 Jun 2022
Cited by 23 | Viewed by 2779
Abstract
(1) Background: The present study aimed to prepare chitosan-coated nanoemulsion gel containing 5-fluorouracil for enhanced topical delivery. (2) Methods: To formulate the nanoemulsion gel, oleic acid was used as the oil phase and Carbopol 940 as a gelling agent. Chitosan was used as [...] Read more.
(1) Background: The present study aimed to prepare chitosan-coated nanoemulsion gel containing 5-fluorouracil for enhanced topical delivery. (2) Methods: To formulate the nanoemulsion gel, oleic acid was used as the oil phase and Carbopol 940 as a gelling agent. Chitosan was used as a coating agent to control the release of 5-FU. Drug–excipient compatibility was evaluated using ATR-FTIR. The prepared nanoemulsion formulations were characterized based on particle size distribution, zeta potential, % encapsulation efficiency and drug content. In vitro drug release, skin drug retention and ex vivo permeation profiles were performed across rat skin using a Franz diffusion cell. Skin irritation experiments were also conducted on rats to examine the irritation potential of the formulations. (3) Results: It was found that the drug and excipients were compatible and chitosan successfully coated 5-FU, as demonstrated by ATR-FTIR results. The introduction of chitosan increased the size and zeta potential of the nanoemulsion. The 5-FU release in vitro was significantly lowered in the case of chitosan-decorated nanoemulsion (5-FU-C-NE), whereas the permeation and skin drug retention were higher in the case of 5-FU-C-NE. The formulations were proven non-irritant to the skin of the rats. The optimized formulation of the nanoemulsion was introduced into 1% Carbopol 940 gel. Incorporating the nanoemulsion into the gel further reduced the drug release in vitro and ex vivo permeation, whereas the retention of the drug in the skin was significantly increased (ANOVA; p < 0.05). The increase in skin retention was due to the presence of chitosan and Carbopol 940. The in vitro and ex vivo results were also confirmed with in vivo studies. Incorporating nanoemulsion into gel has resulted in higher Tmax, longer half-life and greater skin drug retention. (4) Conclusion: The results suggest that chitosan-decorated nanoemulsion gel is safe and can potentially be used to promote 5-FU skin retention, which is ideal for skin diseases such as melanoma. Full article
(This article belongs to the Special Issue Advanced Hydrogels for Controlled Drug Delivery)
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11 pages, 1660 KiB  
Article
Formulation Development and Ex-Vivo Permeability of Curcumin Hydrogels under the Influence of Natural Chemical Enhancers
by Asif Nawaz, Arshad Farid, Muhammad Safdar, Muhammad Shahid Latif, Shakira Ghazanfar, Nosheen Akhtar, Soad K. Al Jaouni, Samy Selim and Muhammad Waseem Khan
Gels 2022, 8(6), 384; https://doi.org/10.3390/gels8060384 - 16 Jun 2022
Cited by 19 | Viewed by 2893
Abstract
Background: The aim of the present research was to formulate and evaluate curcumin hydrogel and to investigate the potential of natural essential oils as permeation enhancers. Methods: Curcumin 2% w/w hydrogel containing various concentrations of eucalyptus oil, aloe vera oil and [...] Read more.
Background: The aim of the present research was to formulate and evaluate curcumin hydrogel and to investigate the potential of natural essential oils as permeation enhancers. Methods: Curcumin 2% w/w hydrogel containing various concentrations of eucalyptus oil, aloe vera oil and clove oil was developed using carboxy methyl cellulose (CMC) as a gelling agent. Differential scanning calorimetry and Fourier Transform infrared spectroscopy were used to evaluate the compatibility between the drug and the excipients. In order to assess the efficacy of the formulation; rheological properties, skin irritation studies, in vitro release, ex vivo permeation and retention studies were conducted. Results: DSC and FTIR suggest no in-compatibility between curcumin and excipients. Studies proved that addition of suitable natural permeation enhancers to the hydrogels improved the in vitro release and ex vivo permeation and retention of curcumin. From the various natural essential oils, the aloe vera oil at a concentration of 3% w/w had the greatest effect on the permeability rate and skin retention of the Curcumin and produces the highest enhancement ratio amongst all the concentrations of essential oils examined. Conclusion: Aloe vera oil enhances the permeation of curcumin across the skin by altering the complex structure of the stratum corneum without itself undergoing any change. The developed curcumin hydrogels along with natural essential oils may present an effective choice regarding skin infection/wound healing. Full article
(This article belongs to the Special Issue Advanced Hydrogels for Controlled Drug Delivery)
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Review

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21 pages, 3044 KiB  
Review
Advances in Nanogels for Topical Drug Delivery in Ocular Diseases
by Yongkang Wu, Qing Tao, Jing Xie, Lili Lu, Xiuli Xie, Yang Zhang and Yong Jin
Gels 2023, 9(4), 292; https://doi.org/10.3390/gels9040292 - 2 Apr 2023
Cited by 20 | Viewed by 4070
Abstract
Nanotechnology has accelerated the development of the pharmaceutical and medical technology fields, and nanogels for ocular applications have proven to be a promising therapeutic strategy. Traditional ocular preparations are restricted by the anatomical and physiological barriers of the eye, resulting in a short [...] Read more.
Nanotechnology has accelerated the development of the pharmaceutical and medical technology fields, and nanogels for ocular applications have proven to be a promising therapeutic strategy. Traditional ocular preparations are restricted by the anatomical and physiological barriers of the eye, resulting in a short retention time and low drug bioavailability, which is a significant challenge for physicians, patients, and pharmacists. Nanogels, however, have the ability to encapsulate drugs within three-dimensional crosslinked polymeric networks and, through specific structural designs and distinct methods of preparation, achieve the controlled and sustained delivery of loaded drugs, increasing patient compliance and therapeutic efficiency. In addition, nanogels have higher drug-loading capacity and biocompatibility than other nanocarriers. In this review, the main focus is on the applications of nanogels for ocular diseases, whose preparations and stimuli-responsive behaviors are briefly described. The current comprehension of topical drug delivery will be improved by focusing on the advances of nanogels in typical ocular diseases, including glaucoma, cataracts, dry eye syndrome, and bacterial keratitis, as well as related drug-loaded contact lenses and natural active substances. Full article
(This article belongs to the Special Issue Advanced Hydrogels for Controlled Drug Delivery)
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