Novel Functional Gels for Biomedical Applications

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

Deadline for manuscript submissions: 15 January 2025 | Viewed by 13236

Special Issue Editor


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Guest Editor
Wenzhou Key Laboratory of Biophysics, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325000, China
Interests: cancer immunotherapy; drug delivery; cell therapy; nanomedicine; biomaterials; gels

Special Issue Information

Dear Colleagues,

Hydrogels represent an emerging frontier in medical research and a promising advancement in drug delivery, tissue regeneration, and disease diagnosis. The rapid progression of such applications, which include hydrogel-based cancer therapy, regulation of inflammatory microenvironments, and tissue repair, has sparked a pressing need for fresh perspectives and innovations in functional gel design.

Both naturally derived and synthetic hydrogels can be tailored to deliver therapeutic drugs or biomolecules, enhancing the treatment of various diseases. While numerous responsive hydrogel systems have been developed for in vivo applications, in vivo treatment results and preclinical applications indicate that there is still ample room for optimization within existing hydrogel systems.

This Special Issue aims to cultivate an avenue for technological advancement and the development of novel functional gels for drug delivery and associated applications. We warmly invite submissions of both research and review articles that focus on cutting-edge technology and functional gels.

Potential topics of interest include, but are not limited to:

  • Hydrogels for cancer immunotherapy;
  • Hydrogels for disease diagnosis;
  • Advanced hydrogel-based drug delivery systems.

Dr. Jilong Wang
Guest Editor

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Keywords

  • gels
  • biomimetic gels
  • drug delivery
  • inflammatory microenvironment regulation
  • cancer therapy

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Published Papers (8 papers)

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Research

18 pages, 6137 KiB  
Article
Decellularized Macroalgae as Complex Hydrophilic Structures for Skin Tissue Engineering and Drug Delivery
by Andreea Luca, Florina-Daniela Cojocaru, Maria Stella Pascal, Teodora Vlad, Isabella Nacu, Catalina Anisoara Peptu, Maria Butnaru and Liliana Verestiuc
Gels 2024, 10(11), 704; https://doi.org/10.3390/gels10110704 - 31 Oct 2024
Viewed by 532
Abstract
Due to their indisputable biocompatibility and abundant source, biopolymers are widely used to prepare hydrogels for skin tissue engineering. Among them, cellulose is a great option for this challenging application due to its increased water retention capacity, mechanical strength, versatility and unlimited availability. [...] Read more.
Due to their indisputable biocompatibility and abundant source, biopolymers are widely used to prepare hydrogels for skin tissue engineering. Among them, cellulose is a great option for this challenging application due to its increased water retention capacity, mechanical strength, versatility and unlimited availability. Since algae are an unexploited source of cellulose, the novelty of this study is the decellularization of two different species, freshly collected from the Black Sea coast, using two different chemical surfactants (sodium dodecyl sulphate and Triton X-100), and characterisation of the resulted complex biopolymeric 3D matrices. The algae nature and decellularization agent significantly influenced the matrices porosity, while the values obtained for the hydration degree included them in hydrogel class. Moreover, their capacity to retain and then controllably release an anti-inflammatory drug, ibuprofen, led us to recommend the obtained structures as drug delivery systems. The decellularized macroalgae hydrogels are bioadhesive and cytocompatible in direct contact with human keratinocytes and represent a great support for cells. Finally, it was noticed that human keratinocytes (HaCaT cell line) adhered and populated the structures during a monitoring period of 14 days. Full article
(This article belongs to the Special Issue Novel Functional Gels for Biomedical Applications)
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14 pages, 2854 KiB  
Article
The Preparation and Evaluation of a Hydrochloride Hydrogel Patch with an Iontophoresis-Assisted Release of Terbinafine for Transdermal Delivery
by Mengfei Li, Xinghao Chen, Xiangxiang Su and Wenyan Gao
Gels 2024, 10(7), 456; https://doi.org/10.3390/gels10070456 - 12 Jul 2024
Viewed by 1102
Abstract
Background: Terbinafine hydrochloride (TEB) is a broad-spectrum antifungal medication commonly used to treat fungal infections of the skin. This study designed a hydrogel patch assisted by an iontophoresis system to enhance the transdermal permeability of TEB, enabling deeper penetration into the skin layers. [...] Read more.
Background: Terbinafine hydrochloride (TEB) is a broad-spectrum antifungal medication commonly used to treat fungal infections of the skin. This study designed a hydrogel patch assisted by an iontophoresis system to enhance the transdermal permeability of TEB, enabling deeper penetration into the skin layers. Methods: The influences of current intensity, pH levels, and drug concentration on the TEB hydrogel patch’s permeability were explored using an adaptive ion electroosmosis system. The pharmacokinetic profile, facilitated by iontophoresis for transdermal permeation, was analyzed through the application of microdialysis technology. Scanning electron microscopy and transmission electron microscopy were employed to assess the impact of ion electroosmotic systems on skin integrity. Results: The cumulative drug accumulation within 8 h of the TEB hydrogel patches, assisted by iontophoresis, was 2.9 and 7.9 times higher than without iontophoresis assistance and TEB cream in the control group, respectively. TEB hydrogel patches assisted by iontophoresis can significantly increase the permeability of TEB, and the AUC(0–8 h) was 3.4 and 5.4 times higher, while the Cmax was 4.2 and 7.3 times higher than the TEB hydrogel patches without iontophoresis, respectively. This system has no significant impact on deep-layer cells. Conclusions: This system may offer a safe and effective clinical strategy for the local treatment of deep antifungal infections. Full article
(This article belongs to the Special Issue Novel Functional Gels for Biomedical Applications)
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12 pages, 1603 KiB  
Article
Mucoadhesive Pharmacology: Latest Clinical Technology in Antiseptic Gels
by María Baus-Domínguez, Felipe-Rodrigo Aguilera, Fernando Vivancos-Cuadras, Lourdes Ferra-Domingo, Daniel Torres-Lagares, José-Luis Gutiérrez-Pérez, Tanya Pereira-Riveros, Teresa Vinuesa and María-Ángeles Serrera-Figallo
Gels 2024, 10(1), 23; https://doi.org/10.3390/gels10010023 - 26 Dec 2023
Cited by 3 | Viewed by 1553
Abstract
Chlorhexidine (CHX) is one of the most widely used antiseptics in the oral cavity due to its high antimicrobial potential. However, many authors have stated that the effect of CHX in nonsurgical periodontal therapy is hampered by its rapid elimination from the oral [...] Read more.
Chlorhexidine (CHX) is one of the most widely used antiseptics in the oral cavity due to its high antimicrobial potential. However, many authors have stated that the effect of CHX in nonsurgical periodontal therapy is hampered by its rapid elimination from the oral environment. The aim of this study was to determine the antibacterial efficacy of a new compound of chlorhexidine 0.20% + cymenol (CYM) 0.10% on a multispecies biofilm. For this, an in vitro study was designed using a multispecies biofilm model of Streptococcus mutans, Fusobacterium nucleatum, Prevotella intermedia, and Porphyromonas gingivalis. Quantification of the microbial viability of the biofilm was performed using 5-cyano-2,3-ditolyl tetrazolium-chloride (CTC) to calculate the percentage of survival, and the biofilms were observed using a a confocal laser scanning microscopy (CLSM). It was observed that the bactericidal activity of the CHX + cymenol bioadhesive gel was superior to that of the CHX bioadhesive gel, in addition to higher penetrability into the biofilm. Therefore, there was greater elimination of bacterial biofilm with the new compound of chlorhexidine 0.2% plus cymenol 0.1% in a bioadhesive gel form compared to the formulation with only chlorhexidine 0.2% in a bioadhesive gel form. Full article
(This article belongs to the Special Issue Novel Functional Gels for Biomedical Applications)
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16 pages, 3067 KiB  
Article
Preparation and Optimization of Bovine Serum Albumin Nanoparticles as a Promising Gelling System for Enhanced Nasal Drug Administration
by Sandra Aulia Mardikasari, Gábor Katona, Bence Sipos, Rita Ambrus and Ildikó Csóka
Gels 2023, 9(11), 896; https://doi.org/10.3390/gels9110896 - 13 Nov 2023
Cited by 5 | Viewed by 1958
Abstract
Bovine serum albumin (BSA) has been used extensively as a suitable carrier system for alternative drug delivery routes, such as nasal administration. However, the optimization of BSA nanoparticles with respect to their nasal applicability has not been widely studied. The present study focuses [...] Read more.
Bovine serum albumin (BSA) has been used extensively as a suitable carrier system for alternative drug delivery routes, such as nasal administration. However, the optimization of BSA nanoparticles with respect to their nasal applicability has not been widely studied. The present study focuses on the characterization of BSA nanoparticles prepared using the desolvation method, followed by a gelation process to facilitate intranasal drug delivery. The results demonstrated that the ratio of BSA and the desolvating agent, ethanol, played a critical role in the nanoparticle characteristics of the BSA nanogel matrices (BSA-NGs). Based on the gelling properties, the formulations of BSA-NG 2, BSA-NG 4, and BSA-NG 6 were selected for further investigation. The Raman spectra confirmed that there were no specific changes to the secondary structures of the BSA. The mucoadhesion studies revealed moderately high mucoadhesive properties, with a mucin binding efficiency (MBE) value of around 67%, allowing the dose to avoid elimination due to rapid mucociliary clearance of the nasal passage. Via studying the nexus of the carrier system, BSA-NGs loaded with dexamethasone as a model drug were prepared and evaluated by differential scanning calorimetry (DSC) and thermal gravimetry (TG), ascertaining that no ethanol remained in the samples after the freeze-drying process. Furthermore, the viscosity measurements exhibited moderate viscosity, which is suitable for nasal liquid preparations. The in vitro release studies performed with a simulated nasal electrolyte solution (SNES) medium showed 88.15–95.47% drug release within 4 h. In conclusion, BSA nanoparticle gelling matrices can offer potential, value-added drug delivery carriers for improved nasal drug administration. Full article
(This article belongs to the Special Issue Novel Functional Gels for Biomedical Applications)
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22 pages, 4316 KiB  
Article
Gelled Liquid Crystal Nanocarriers for Improved Antioxidant Activity of Resveratrol
by Antonia Mancuso, Martine Tarsitano, Rosy Cavaliere, Massimo Fresta, Maria Chiara Cristiano and Donatella Paolino
Gels 2023, 9(11), 872; https://doi.org/10.3390/gels9110872 - 2 Nov 2023
Cited by 1 | Viewed by 1880
Abstract
As many natural origin antioxidants, resveratrol is characterized by non-suitable physicochemical properties for its topical application. To allow its benefits to manifest on human skin, resveratrol has been entrapped within liquid crystal nanocarriers (LCNs) made up of glyceryl monooleate, a penetration enhancer, and [...] Read more.
As many natural origin antioxidants, resveratrol is characterized by non-suitable physicochemical properties for its topical application. To allow its benefits to manifest on human skin, resveratrol has been entrapped within liquid crystal nanocarriers (LCNs) made up of glyceryl monooleate, a penetration enhancer, and DSPE-PEG 750. The nanosystems have been more deeply characterized by using dynamic light scattering and Turbiscan Lab® Expert optical analyzer, and they have been tested in vitro on NCTC 2544. The improved antioxidant activity of entrapped resveratrol was evaluated on keratinocyte cells as a function of its concentration. Finally, to really propose the resveratrol-loaded LCNs for topical use, the systems were gelled by using two different gelling agents, poloxamer P407 and carboxymethyl cellulose, to improve the contact time between skin and formulation. The rheological features of obtained gels were evaluated using two important methods (microrheology at rest and dynamic rheology), before testing their safety profile on human healthy volunteers. The obtained results showed the ability of LCNs to improve antioxidant activity of RSV and the gelled LCNs showed good rheological profiles. In conclusion, the results confirmed the potentiality of gelled resveratrol-loaded nanosystems for skin disease, mainly related to their antioxidant effects. Full article
(This article belongs to the Special Issue Novel Functional Gels for Biomedical Applications)
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23 pages, 5665 KiB  
Article
In Situ Forming Bioartificial Hydrogels with ROS Scavenging Capability Induced by Gallic Acid Release with Potential in Chronic Skin Wound Treatment
by Rossella Laurano, Alessandro Torchio, Gianluca Ciardelli and Monica Boffito
Gels 2023, 9(9), 731; https://doi.org/10.3390/gels9090731 - 9 Sep 2023
Cited by 2 | Viewed by 1578
Abstract
In normal chronic wound healing pathways, the presence of strong and persistent inflammation states characterized by high Reactive Oxygen Species (ROS) concentrations is one of the major concerns hindering tissue regeneration. The administration of different ROS scavengers has been investigated over the years, [...] Read more.
In normal chronic wound healing pathways, the presence of strong and persistent inflammation states characterized by high Reactive Oxygen Species (ROS) concentrations is one of the major concerns hindering tissue regeneration. The administration of different ROS scavengers has been investigated over the years, but their effectiveness has been strongly limited by their short half-life caused by chronic wound environmental conditions. This work aimed at overcoming this criticism by formulating bioartificial hydrogels able to preserve the functionalities of the encapsulated scavenger (i.e., gallic acid—GA) and expand its therapeutic window. To this purpose, an amphiphilic poly(ether urethane) exposing -NH groups (4.5 × 1020 units/gpolymer) was first synthesized and blended with a low molecular weight hyaluronic acid. The role exerted by the solvent on system gelation mechanism and swelling capability was first studied, evidencing superior thermo-responsiveness for formulations prepared in saline solution compared to double demineralized water (ddH2O). Nevertheless, drug-loaded hydrogels were prepared in ddH2O as the best compromise to preserve GA from degradation while retaining gelation potential. GA was released with a controlled and sustained profile up to 48 h and retained its scavenger capability against hydroxyl, superoxide and 1′-diphenyl-2-picrylhydrazyl radicals at each tested time point. Moreover, the same GA amounts were able to significantly reduce intracellular ROS concentration upon oxidative stress induction. Lastly, the system was highly cytocompatible according to ISO regulation and GA-enriched extracts did not induce NIH-3T3 morphology changes. Full article
(This article belongs to the Special Issue Novel Functional Gels for Biomedical Applications)
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23 pages, 7504 KiB  
Article
Moxifloxacin HCl-Incorporated Aqueous-Induced Nitrocellulose-Based In Situ Gel for Periodontal Pocket Delivery
by Setthapong Senarat, Catleya Rojviriya, Katekeaw Sarunyakasitrin, Juree Charoentreeraboon, Wiwat Pichayakorn and Thawatchai Phaechamud
Gels 2023, 9(7), 572; https://doi.org/10.3390/gels9070572 - 13 Jul 2023
Cited by 4 | Viewed by 2147
Abstract
A drug delivery system based on an aqueous-induced in situ forming gel (ISG) consists of solubilizing the drug within an organic solution of a polymer using a biocompatible organic solvent. Upon contact with an aqueous medium, the solvent diffuses out and the polymer, [...] Read more.
A drug delivery system based on an aqueous-induced in situ forming gel (ISG) consists of solubilizing the drug within an organic solution of a polymer using a biocompatible organic solvent. Upon contact with an aqueous medium, the solvent diffuses out and the polymer, designed to be insoluble in water, solidifies and transforms into gel. Nitrocellulose (Nc), an aqueous insoluble nitrated ester of cellulose, should be a promising polymer for an ISG using water induction of its solution to gel state via phase inversion. The aim of this investigation was to develop and evaluate a moxifloxacin HCl (Mx)-incorporated aqueous-induced Nc-based ISG for periodontitis treatment. The effects of different solvents (N-methyl pyrrolidone (NMP), DMSO, 2-pyrrolidone (Py), and glycerol formal (Gf)) on the physicochemical and bioactivity properties of the ISGs were investigated. The viscosity and injection force of the ISGs varied depending on the solvent used, with Gf resulting in higher values of 4631.41 ± 52.81 cPs and 4.34 ± 0.42 N, respectively. All ISGs exhibited Newtonian flow and transformed into a gel state upon exposure to the aqueous phase. The Nc formulations in DMSO showed lower water tolerance (12.50 ± 0.72%). The developed ISGs were easily injectable and demonstrated water sensitivity of less than 15.44 ± 0.89%, forming a gel upon contact with aqueous phase. The transformed Nc gel effectively prolonged Mx release over two weeks via Fickian diffusion, with reduced initial burst release. Different solvent types influenced the sponge-like 3D structure of the dried Nc ISGs and affected mass loss during drug release. Incorporating Nc reduced both solvent and drug diffusion, resulting in a significantly narrower zone of bacterial growth inhibition (p < 0.05). The Mx-incorporated Nc-based ISGs exhibited efficient antibacterial activity against four strains of Staphylococcus aureu and against periodontitis pathogens including Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis. This study suggests that the developed Mx-incorporated Nc-based ISGs using DMSO and NMP as the solvents are the most promising formulations. They exhibited a low viscosity, ease of injection, and rapid transformation into a gel upon aqueous induction, and they enabled localized and prolonged drug release with effective antibacterial properties. Additionally, this study represents the first reported instance of utilizing Nc as the polymer for ISG. Further clinical experiments are necessary to evaluate the safety of this ISG formulation. Full article
(This article belongs to the Special Issue Novel Functional Gels for Biomedical Applications)
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24 pages, 10390 KiB  
Article
Phase Inversion-Based Doxycycline Hyclate-Incorporated Borneol In Situ Gel for Periodontitis Treatment
by Nutdanai Lertsuphotvanit, Sarun Tuntarawongsa, Takron Chantadee and Thawatchai Phaechamud
Gels 2023, 9(7), 557; https://doi.org/10.3390/gels9070557 - 7 Jul 2023
Cited by 1 | Viewed by 1758
Abstract
Borneol has been successfully employed as a gelling agent for in situ forming gel (ISG). While 40% borneol can regulate drug release, there is interest in novel approaches to achieve extended drug release, particularly through the incorporation of hydrophobic substances. Herein, triacetin was [...] Read more.
Borneol has been successfully employed as a gelling agent for in situ forming gel (ISG). While 40% borneol can regulate drug release, there is interest in novel approaches to achieve extended drug release, particularly through the incorporation of hydrophobic substances. Herein, triacetin was selected as a hydrophobic additive solvent for doxycycline hyclate (Dox)-loaded 40% borneol-based ISGs in N-methyl-2-pyrrolidone (NMP) or dimethyl sulfoxide (DMSO), which were subsequently evaluated in terms of their physicochemical properties, gel formation morphology, water sensitivity, drug release, and antimicrobial activities. ISG density and viscosity gradually decreased with the triacetin proportion to a viscosity of <12 cPs and slightly influenced the surface tension (33.14–44.33 mN/m). The low expelled force values (1.59–2.39 N) indicated the convenience of injection. All of the prepared ISGs exhibited favorable wettability and plastic deformation. Higher gel firmness from ISG prepared using NMP as a solvent contributed to the ability of more efficient controlled drug release. High triacetin (25%)-loaded ISG retarded solvent diffusion and gel formation, but diminished gel firmness and water sensitivity. ISG containing 5% triacetin efficiently prolonged Dox release up to 10 days with Fickian diffusion and presented effective antimicrobial activities against periodontitis pathogens such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. Therefore, the Dox-loaded 40% borneol-based ISG with 5% triacetin is a potential effective local ISG for periodontitis treatment. Full article
(This article belongs to the Special Issue Novel Functional Gels for Biomedical Applications)
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