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Application of Hydrogels in Therapeutics and Theranostics Delivery

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A special issue of Gels (ISSN 2310-2861).

Deadline for manuscript submissions: closed (1 July 2022) | Viewed by 33580

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Special Issue Editor

Dr. Rajendran JC Bose

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Guest Editor

Biomedical and Translational Medicine, Masonic Medical Research Institute, Utica, NY 13501, USA
Interests: nanomaterials; drug and gene delivery; molecular imaging

Special Issue Information

Dear Colleagues,

Systemic administration of therapeutic or theranostic agents has been the preferred approach to diagnose or treat most pathological conditions. However, intravenous administrations are often associated with off-target accumulation causing toxicity and adverse effects. Alternatively, local delivery platforms, such as hydrogels that circumvent the obstacles of systemic delivery, have been emerging. Hydrogels are hydrophilic, three-dimensional networks that can absorb large amounts of water or biological fluids. Hydrogels can provide spatial and temporal control over the release of various therapeutic and theranostic agents, including small-molecule drugs, genes, imaging agents, growth factors, and cells. Local administration of these hydrogels allows delivery of higher “effective” doses while enhancing therapeutic molecules’ stability, minimizing side effects. Hydrogels have proven to be highly biocompatible materials that allow for the customized design to afford sensing and therapy at the same time. Hydrogels’ chemical and physical versatility can be exploited to attain pathological environment-triggered in situ assemblies and programmed degradation and subsequent therapeutics and theragnostic release. Hydrogels are used as reservoirs for diverse therapeutics and theragnostics including small molecules, genes, imaging agents, growth factors, and cells. Hydrogels can provide spatial and temporal control over the release of incorporated therapeutics and theragnostic for a prolonged period, thereby assisting in early disease diagnosis, therapy, and prognosis. Recent advances in polymeric and materials chemistry, biomedicine, and nanoengineering have resulted in numerous innovative developments in the field of hydrogels for therapeutic and theragnostic delivery. However, numerous challenges need to be addressed well for successful bench to bedside translation. Thus, in this “Special Issue”, we invite researchers to contribute their current forays into this important emergent field.

Dr. Rajendran JC Bose
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 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

Smart hydrogels for drug, gene, and imaging agent delivery
Stimuli-responsive hydrogels for drug delivery, tumor imaging, therapy, and nano theragnostics and applications in regenerative medicines
Injectable hydrogels: development, characterization, and biomedical applications

Published Papers (7 papers)

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Research

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21 pages, 4444 KiB

Open AccessArticle

Preparation and Evaluation of Chitosan/PVA Based Hydrogel Films Loaded with Honey for Wound Healing Application

by Hitesh Chopra, Shabana Bibi, Sandeep Kumar, Muhammad Saad Khan, Pradeep Kumar and Inderbir Singh

Gels 2022, 8(2), 111; https://doi.org/10.3390/gels8020111 - 11 Feb 2022

Cited by 62 | Viewed by 8986

Abstract

In the present study, chitosan/polyvinyl alcohol (PVA)-based honey hydrogel films were developed for potential wound healing application. The hydrogel films were developed by a solvent-casting method and were evaluated in terms of thickness, weight variation, folding endurance, moisture content and moisture uptake. The water vapor transmission rate was found to range between 1650.50 ± 35.86 and 2698.65 ± 76.29 g/m²/day. The tensile strength and elongation at break were found to range between 4.74 ± 0.83 and 38.36 ± 5.39 N, and 30.58 ± 3.64 and 33.51 ± 2.47 mm, respectively, indicating significant mechanical properties of the films. SEM images indicated smooth surface morphology of the films. FTIR, DSC and in silico analysis were performed, which highlighted the docking energies of the protein–ligand complex and binding interactions such as hydrogen bonding, Pi–Pi bonding, and Pi–H bonding between the selected compounds and target proteins; hence, we concluded, with the three best molecules (lumichrome, galagin and chitosan), that there was wound healing potential. In vitro studies pointed toward a sustained release of honey from the films. The antimicrobial performance of the films was investigated against Staphylococcus aureus. Overall, the results signaled the potential application of chitosan/PVA based hydrogel films as wound dressings. Furthermore, in vivo experiments may be required to evaluate the clinical efficacy of honey-loaded chitosan/PVA hydrogel films in wound healing. Full article

(This article belongs to the Special Issue Application of Hydrogels in Therapeutics and Theranostics Delivery)

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12 pages, 6369 KiB

Open AccessEditor’s ChoiceArticle

Evaluating the Biocompatibility of an Injectable Wound Matrix in a Murine Model

by Hatem Alnojeidi, Ruhangiz Taghi Kilani and Aziz Ghahary

Gels 2022, 8(1), 49; https://doi.org/10.3390/gels8010049 - 09 Jan 2022

Cited by 4 | Viewed by 1802

Abstract

(1) Background: Developing a high-quality, injectable biomaterial that is labor-saving, cost-efficient, and patient-ready is highly desirable. Our research group has previously developed a collagen-based injectable scaffold for the treatment of a variety of wounds including wounds with deep and irregular beds. Here, we investigated the biocompatibility of our liquid scaffold in mice and compared the results to a commercially available injectable granular collagen-based product. (2) Methods: Scaffolds were applied in sub-dermal pockets on the dorsum of mice. To examine the interaction between the scaffolds and the host tissue, samples were harvested after 1 and 2 weeks and stained for collagen content using Masson’s Trichrome staining. Immunofluorescence staining and quantification were performed to assess the type and number of cells infiltrating each scaffold. (3) Results: Histological evaluation after 1 and 2 weeks demonstrated early and efficient integration of our liquid scaffold with no evident adverse foreign body reaction. This rapid incorporation was accompanied by significant cellular infiltration of stromal and immune cells into the scaffold when compared to the commercial product (p < 0.01) and the control group (p < 0.05). Contrarily, the commercial scaffold induced a foreign body reaction as it was surrounded by a capsule-like, dense cellular layer during the 2-week period, resulting in delayed integration and hampered cellular infiltration. (4) Conclusion: Results obtained from this study demonstrate the potential use of our liquid scaffold as an advanced injectable wound matrix for the management of skin wounds with complex geometries. Full article

(This article belongs to the Special Issue Application of Hydrogels in Therapeutics and Theranostics Delivery)

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13 pages, 1196 KiB

Open AccessArticle

Influence of Bile Acids in Hydrogel Pharmaceutical Formulations on Dissolution Rate and Permeation of Clindamycin Hydrochloride

by Nebojša Pavlović, Isidora Anastasija Bogićević, Dragana Zaklan, Maja Đanić, Svetlana Goločorbin-Kon, Hani Al-Salami and Momir Mikov

Gels 2022, 8(1), 35; https://doi.org/10.3390/gels8010035 - 05 Jan 2022

Cited by 6 | Viewed by 2614

Abstract

Clindamycin hydrochloride is a widely used antibiotic for topical use, but its main disadvantage is poor skin penetration. Therefore, new approaches in the development of clindamycin topical formulations are of great importance. We aimed to investigate the effects of the type of gelling agent (carbomer and sodium carmellose), and the type and concentration of bile acids as penetration enhancers (0.1% and 0.5% of cholic and deoxycholic acid), on clindamycin release rate and permeation in a cellulose membrane in vitro model. Eight clindamycin hydrogel formulations were prepared using a 2³ full factorial design, and they were evaluated for physical appearance, pH, drug content, drug release, and permeability parameters. Although formulations with carbomer as the gelling agent exerted optimal sensory properties, carmellose sodium hydrogels had significantly higher release rates and permeation of clindamycin hydrochloride. The bile acid enhancement factors were higher in carbomer gels, and cholic acid exerted more pronounced permeation-enhancing effects. Since the differences in the permeation parameters of hydrogels containing cholic acid in different concentrations were insignificant, its addition in a lower concentration is more favorable. The hydrogel containing carmellose sodium as a gelling agent and 0.1% cholic acid as a penetration enhancer can be considered as the formulation of choice. Full article

(This article belongs to the Special Issue Application of Hydrogels in Therapeutics and Theranostics Delivery)

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11 pages, 1984 KiB

Open AccessArticle

Use of High-Refractive Index Hydrogels and Tissue Clearing for Large Biological Sample Imaging

by Alexander Richardson, Sandra Fok, Victoria Lee, Kerry-Anne Rye, Nick Di Girolamo and Blake J. Cochran

Gels 2022, 8(1), 32; https://doi.org/10.3390/gels8010032 - 04 Jan 2022

Cited by 2 | Viewed by 1915

Abstract

Recent advances in tissue clearing and light sheet fluorescence microscopy have improved insights into and understanding of tissue morphology and disease pathology by imaging large samples without the requirement of histological sectioning. However, sample handling and conservation of sample integrity during lengthy staining and acquisition protocols remains a challenge. This study overcomes these challenges with acrylamide hydrogels synthesised to match the refractive index of solutions typically utilised in aqueous tissue clearing protocols. These hydrogels have a high-water content (82.0 ± 3.7% by weight). The gels are stable over time and FITC-IgG readily permeated into and effluxed out of them. Whilst the gels deformed and/or swelled over time in some commonly used solutions, this was overcome by using a previously described custom refractive index matched solution. To validate their use, CUBIC cleared mouse tissues and whole embryos were embedded in hydrogels, stained using fluorescent small molecule dyes, labels and antibodies and successfully imaged using light sheet fluorescence microscopy. In conclusion, the high water content, high refractive index hydrogels described in this study have broad applicability to research that delves into pathophysiological processes by stabilising and protecting large and fragile samples. Full article

(This article belongs to the Special Issue Application of Hydrogels in Therapeutics and Theranostics Delivery)

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15 pages, 3335 KiB

Open AccessArticle

Poly(2-Hydroxyethyl methacrylate-co-N,N-dimethylacrylamide)-Coated Quartz Crystal Microbalance Sensor: Membrane Characterization and Proof of Concept

by Angel Ramon Hernandez-Martinez

Gels 2021, 7(4), 151; https://doi.org/10.3390/gels7040151 - 24 Sep 2021

Cited by 4 | Viewed by 2536

Abstract

Application-oriented hydrogel properties can be obtained by modifying the synthesis conditions of the materials. The purpose of this study is to achieve customized properties for sensing applications of hydrogel membranes based on poly(2-hydroxyethyl methacrylate), HEMA and N,N-dimethylacrylamide, DMAa. Copolymer p(HEMA-co-DMAa) hydrogels were prepared by varying the DMAa monomer ratio from 0–100% in 20% increments. Hydrogel membranes were characterized by attenuated infrared spectroscopy. Swelling and sorption were evaluated using cation solutions. Copolymers were also synthesized on the gold surface of quartz crystal microbalances (QCM) as coating membranes. A proof of concept was conducted for approaching the design and development of QCM sensors based on P(DMAa-co-HEMA)-membranes. Results showed that the water and ion adsorption capacity of hydrogel membranes increased with higher DMAa content. Membranes are not selective to a specific location but did show different transport features with each cation. The QCM coated with the selected membrane presented linear relationships between resonance frequency and ions concentration in solution (10–120 ppm). As a consequence, hydrogel membranes obtained are promising for the development of future biosensing devices. Full article

(This article belongs to the Special Issue Application of Hydrogels in Therapeutics and Theranostics Delivery)

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Review

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50 pages, 4966 KiB

Open AccessReview

Drug Delivery Challenges and Current Progress in Nanocarrier-Based Ocular Therapeutic System

by Md Habban Akhter, Irfan Ahmad, Mohammad Y. Alshahrani, Alhanouf I. Al-Harbi, Habibullah Khalilullah, Obaid Afzal, Abdulmalik S. A. Altamimi, Shehla Nasar Mir Najib Ullah, Abhijeet Ojha and Shahid Karim

Gels 2022, 8(2), 82; https://doi.org/10.3390/gels8020082 - 28 Jan 2022

Cited by 45 | Viewed by 9555

Abstract

Drug instillation via a topical route is preferred since it is desirable and convenient due to the noninvasive and easy drug access to different segments of the eye for the treatment of ocular ailments. The low dose, rapid onset of action, low or no toxicity to the local tissues, and constrained systemic outreach are more prevalent in this route. The majority of ophthalmic preparations in the market are available as conventional eye drops, which rendered <5% of a drug instilled in the eye. The poor drug availability in ocular tissue may be attributed to the physiological barriers associated with the cornea, conjunctiva, lachrymal drainage, tear turnover, blood–retinal barrier, enzymatic drug degradation, and reflex action, thus impeding deeper drug penetration in the ocular cavity, including the posterior segment. The static barriers in the eye are composed of the sclera, cornea, retina, and blood–retinal barrier, whereas the dynamic barriers, referred to as the conjunctival and choroidal blood flow, tear dilution, and lymphatic clearance, critically impact the bioavailability of drugs. To circumvent such barriers, the rational design of the ocular therapeutic system indeed required enriching the drug holding time and the deeper permeation of the drug, which overall improve the bioavailability of the drug in the ocular tissue. This review provides a brief insight into the structural components of the eye as well as the therapeutic challenges and current developments in the arena of the ocular therapeutic system, based on novel drug delivery systems such as nanomicelles, nanoparticles (NPs), nanosuspensions, liposomes, in situ gel, dendrimers, contact lenses, implants, and microneedles. These nanotechnology platforms generously evolved to overwhelm the troubles associated with the physiological barriers in the ocular route. The controlled-drug-formulation-based strategic approach has considerable potential to enrich drug concentration in a specific area of the eye. Full article

(This article belongs to the Special Issue Application of Hydrogels in Therapeutics and Theranostics Delivery)

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29 pages, 1143 KiB

Open AccessEditor’s ChoiceReview

Inherent and Composite Hydrogels as Promising Materials to Limit Antimicrobial Resistance

by Rahela Carpa, Alexei Remizovschi, Carla Andreea Culda and Anca Livia Butiuc-Keul

Gels 2022, 8(2), 70; https://doi.org/10.3390/gels8020070 - 20 Jan 2022

Cited by 33 | Viewed by 5143

Abstract

Antibiotic resistance has increased significantly in the recent years, and has become a global problem for human health and the environment. As a result, several technologies for the controlling of health-care associated infections have been developed over the years. Thus, the most recent findings in hydrogel fabrication, particularly antimicrobial hydrogels, could offer valuable solutions for these biomedical challenges. In this review, we discuss the most promising strategies in the development of antimicrobial hydrogels and the application of hydrogels in the treatment of microbial infections. The latest advances in the development of inherently and composite antimicrobial hydrogels will be discussed, as well as hydrogels as carriers of antimicrobials, with a focus on antibiotics, metal nanoparticles, antimicrobial peptides, and biological extracts. The emergence of CRISR-Cas9 technology for removing the antimicrobial resistance has led the necessity of new and performant carriers for delivery of the CRISPR-Cas9 system. Different delivery systems, such as composite hydrogels and many types of nanoparticles, attracted a great deal of attention and will be also discussed in this review. Full article

(This article belongs to the Special Issue Application of Hydrogels in Therapeutics and Theranostics Delivery)

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