Hydrogels For Drug Delivery Research Articles

Controlled delivery of gold nanoparticle-coupled miRNA therapeutics via an injectable self-healing hydrogel.

Differential expression of microRNAs (miRNAs) plays a role in many diseases, including cancer and cardiovascular diseases. Potentially, miRNAs could be targeted with miRNA-therapeutics. Sustained delivery of these therapeutics remains challenging. This study couples miR-mimics to PEG-peptide gold nanoparticles (AuNP) and loads these AuNP-miRNAs in an injectable, shear thinning, self-assembling polymer nanoparticle (PNP) hydrogel drug delivery platform to improve delivery. Spherical AuNPs coated with fluorescently labelled miR-214 are loaded into an HPMC-PEG-b-PLA PNP hydrogel. Release of AuNP/miRNAs is quantified, AuNP-miR-214 functionality is shown in vitro in HEK293 cells, and AuNP-miRNAs are tracked in a 3D bioprinted human model of calcific aortic valve disease (CAVD). Lastly, biodistribution of PNP-AuNP-miR-67 is assessed after subcutaneous injection in C57BL/6 mice. AuNP-miRNA release from the PNP hydrogel in vitro demonstrates a linear pattern over 5 days up to 20%. AuNP-miR-214 transfection in HEK293 results in 33% decrease of Luciferase reporter activity. In the CAVD model, AuNP-miR-214 are tracked into the cytoplasm of human aortic valve interstitial cells. Lastly, 11 days after subcutaneous injection, AuNP-miR-67 predominantly clears via the liver and kidneys, and fluorescence levels are again comparable to control animals. Thus, the PNP-AuNP-miRNA drug delivery platform provides linear release of functional miRNAs in vitro and has potential for in vivo applications.

Custom-design of intrinsically antimicrobial polyurethane hydrogels as multifunctional injectable delivery systems for mini-invasive wound treatment

• Infections represent the major obstacle hindering the healing of chronic wounds. • The development of polymers intrinsically antimicrobial reduces the need of antibiotics. • The chemical versatility of polyurethanes results in polymers with ad-hoc properties. • System thermosensitivity allows shape-adaptability and rapid post-injection gelation. • The micellar hydrogel network opens the way to versatile delivery carriers. Effective management of hard-to-close skin wounds is a challenging issue due to several co-morbidities in affected patients. Particularly, infections represent a major obstacle in wound healing. The design of efficient wound treatments thus represents an urgent need. Injectable drug delivery hydrogels with intrinsic antimicrobial and antifungal properties were herein designed for perspective application in the mini-invasive treatment of hard-to-close wounds. First, an amphiphilic polyurethane was synthesized from Poloxamer® 407 macrodiol and N-Boc diethanolamine chain extender (DHP407, M ¯ w =33 kDa). Chain-extension reaction step was optimized to maximize the formation of -NH groups along the polymer chains (4.5 × 10 20 ±1.8 × 10 19 –NH groups/g polymer ), after Boc-caging group removal (D-DHP407). DHP407 and D-DHP407 water-based solutions were thermosensitive with slightly different Critical Micellar Concentration (17.5 μg/mL vs . 19.7 μg/mL) and cluster hydrodynamic diameter (235.6 ± 19.9 nm vs . 260.1 ± 20.5 nm), and similar Critical Micellar Temperature (22.5 °C vs . 23.1 °C). A polyurethane solution concentration (15% w/V) was selected by tube-inverting test and rheological analysis showing injectability, as evidenced by sol-to-gel transition at 27.7 ± 0.6 °C for DHP407 and 29.7 ± 0.6 °C for D-DHP407, within few minutes, at similar gelation kinetics. DHP407 and D-DHP407 hydrogels showed controlled release of Bovine Serum Albumin (BSA) model protein (1 mg/mL), with no burst phenomena. BSA released from DHP407 and D-DHP407 hydrogels at 24 h was 33.7 ± 5.0% and 24.6 ± 1.2%, respectively. D-DHP407 hydrogel was biocompatible and able to support NIH-3T3 cell proliferation. Furthermore, D-DHP407 hydrogel showed intrinsic antifungal and antibacterial activity against C. albicans and Gram-positive S. aureus and Gram-negative E. coli bacteria, injectability and capability to retain shape post-injection, making it promising for future use in the management of hard-to-close skin wounds.

Hydrogels Based on Poly(Ether-Ester)s as Highly Controlled 5-Fluorouracil Delivery Systems-Synthesis and Characterization.

A novel and promising hydrogel drug delivery system (DDS) capable of releasing 5‑fluorouracil (5-FU) in a prolonged and controlled manner was obtained using ε‑caprolactone‑poly(ethylene glycol) (CL-PEG) or rac‑lactide-poly(ethylene glycol) (rac‑LA-PEG) copolymers. Copolymers were synthesized via the ring-opening polymerization (ROP) process of cyclic monomers, ε‑caprolactone (CL) or rac-lactide (rac-LA), in the presence of zirconium(IV) octoate (Zr(Oct)4) and poly(ethylene glycol) 200 (PEG 200) as catalyst and initiator, respectively. Obtained triblock copolymers were characterized by nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC) techniques; the structure and tacticity of the macromolecules were determined. The relationship between the copolymer structure and the reaction conditions was evaluated. The optimal conditions were specified as 140 °C and 24 h. In the next step, CL-PEG and rac-LA-PEG copolymers were chemically crosslinked using hexamethylene diisocyanate (HDI). Selected hydrogels were subjected to in vitro antitumor drug release studies, and the release data were analyzed using zero-order, first-order, and Korsmeyer-Peppas mathematical models. Controlled and prolonged (up to 432 h) 5-FU release profiles were observed for all examined hydrogels with first-order or zero-order kinetics. The drug release mechanism was generally denoted as non-Fickian transport.

Influence of pH-responsive compounds synthesized from chitosan and hyaluronic acid on dual-responsive (pH/temperature) hydrogel drug delivery systems of Cortex Moutan

The polysaccharide-based pH-responsive compounds, namely, N,N,N-trimethyl chitosan (TMC), polyethylene glycolated hyaluronic acid (PEG-HA), and polysaccharide-based nano-conjugate of hyaluronic acid, chitosan oligosaccharide and alanine [HA-Ala-Chito(oligo)] were chemically synthesized using biopolymers chitosan and hyaluronic acid, and applied here to observe the changes in morphology, pH-stability, mechanical and drug-release behavior, and cytotoxicity of thermo-responsive polymer: Poloxamer 407 (PF127)-based drug delivery systems for traditional Chinese medicine Cortex Moutan (CM). The thermo-responsive hydrogel of PF127 loaded with CM (GelC) was used as control. The dual-responsive (pH/temperature) hydrogels: PF127/TMC/PEG-HA (Gel1) and PF127/HA-Ala-Chito(oligo) (Gel2) showed improved mechanical behavior as obtained by rheology and mechanical agitation study, and pH-stability under various external pH conditions, and those improvements occurred due to the addition of polysaccharide-based pH-responsive compounds in the systems. Both, Gel1 and Gel2 showed better morphology than GelC as obtained by SEM or TEM suggesting that interaction of polysaccharide-based pH-responsive compounds with PF127 in either gel or sol state gave better porous network structure in the hydrogels or more dispersed micellar arrangements in sol-state, respectively. Gel1 showed the highest cumulative drug release (86.5%) after 5 days under mild acidic condition (pH 6.4) suggesting that release behavior of a hydrogel drug carrier was dependent on morphology, mechanical behavior, and pH-stability. The transdermal release (ex-vivo) results indicated that gallic acid, the active marker of CM passed through porcine ear skin and all the formulations showed more or less similar transdermal release properties. The hydrogels loaded with CM showed no cytotoxicity (cell viability >90.0%) on human HaCaT keratinocytes within concentration range of 0.0–20.0 μg/ml as obtained by MTT assay, and cell viability was more than 100% at a concentration of 20.0 μg/ml for Gel2. The formulations without loaded drug namely, Gel1-CM and Gel2-CM exhibited strong anti-bacterial action against gram positive bacteria Staphylococcus aureus.

Hydrogels as Drug Delivery Systems: A Review of Current Characterization and Evaluation Techniques.

Owing to their tunable properties, controllable degradation, and ability to protect labile drugs, hydrogels are increasingly investigated as local drug delivery systems. However, a lack of standardized methodologies used to characterize and evaluate drug release poses significant difficulties when comparing findings from different investigations, preventing an accurate assessment of systems. Here, we review the commonly used analytical techniques for drug detection and quantification from hydrogel delivery systems. The experimental conditions of drug release in saline solutions and their impact are discussed, along with the main mathematical and statistical approaches to characterize drug release profiles. We also review methods to determine drug diffusion coefficients and in vitro and in vivo models used to assess drug release and efficacy with the goal to provide guidelines and harmonized practices when investigating novel hydrogel drug delivery systems.

Multi-stimuli-responsive, liposome-crosslinked poly(ethylene glycol) hydrogels for drug delivery

The development of hybrid hydrogels has been of great interest over recent decades, especially in the field of biomaterials. Such hydrogels provide various opportunities in tissue engineering, drug delivery, and regenerative medicine due to their ability to mimic cellular environments, sequester and release therapeutic agents, and respond to stimuli. Herein we report the synthesis and characterization of an injectable poly(ethylene glycol) hydrogel crosslinked via thiol-maleimide reactions and containing both chemically crosslinked temperature-sensitive liposomes (TSLs) and matrix metalloproteinase-sensitive peptide crosslinks. Rheological studies demonstrate that the hydrogel is mechanically stable and can be synthesized to achieve a range of physically applicable moduli. Experiments characterizing the in situ drug delivery and degradation of these materials indicate that the TSL gel responds to both thermal and enzymatic stimuli in a local environment. Doxorubicin, a widely used anticancer drug, was loaded in the TSLs with a high encapsulation efficiency and the subsequent release was temperature dependent. Finally, TSLs did not compromise viability and proliferation of human and murine fibroblasts, supporting the use of these hydrogel-linked liposomes as a thermo-responsive drug carrier for controlled release.

Carboxymethyl chitosan microspheres loaded hyaluronic acid/gelatin hydrogels for controlled drug delivery and the treatment of inflammatory bowel disease

A major drawback of oral treatment of inflammatory bowel disease (IBD) is the non-specific distribution of drugs during long-term treatment. Despite its effectiveness as an anti-inflammatory drug, curcumin (CUR) is limited by its low bioavailability in IBD treatment. Herein, a pH-sensitive composite hyaluronic acid/gelatin (HA/GE) hydrogel drug delivery system containing carboxymethyl chitosan (CC) microspheres loaded with CUR was fabricated for IBD treatment. The composition and structure of the composite system were optimized and the physicochemical properties were characterized using infrared spectroscopy, X-ray diffraction, swelling, and release behavior studies. In vitro, the formulation exhibited good sustained release property and the drug release rate was 65% for 50 h. In vivo pharmacokinetic experiments indicated that high level of CUR was maintained in the colon tissue for more than 24 h; it also played an anti-inflammatory role by evaluating the histopathological changes through hematoxylin and eosin (H&E), myeloperoxidase (MPO), and immunofluorescent staining. Additionally, the formulation substantially inhibited the level of the main pro-inflammatory cytokines of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) secreted by macrophages, compared to the control group. The pharmacodynamic experiment showed that the formulation group of CUR@gels had the best therapeutic effect on colitis in mice. The composite gel delivery system has potential for the effective delivery of CUR in the treatment of colitis. This study also provides a reference for the design and preparation of a new oral drug delivery system with controlled release behavior.

Optimization of hyaluronic acid-tyramine/silk-fibroin composite hydrogels for cartilage tissue engineering and delivery of anti-inflammatory and anabolic drugs

Injury of articular cartilage leads to an imbalance in tissue homeostasis, and due to the poor self-healing capacity of cartilage the affected tissue often exhibits osteoarthritic changes. In recent years, injectable and highly tunable composite hydrogels for cartilage tissue engineering and drug delivery have been introduced as a desirable alternative to invasive treatments. In this study, we aimed to formulate injectable hydrogels for drug delivery and cartilage tissue engineering by combining different concentrations of hyaluronic acid-tyramine (HA-Tyr) with regenerated silk-fibroin (SF) solutions. Upon enzymatic crosslinking, the gelation and mechanical properties were characterized over time. To evaluate the effect of the hydrogel compositions and properties on extracellular matrix (ECM) deposition, bovine chondrocytes were embedded in enzymatically crosslinked HA-Tyr/SF composites (in further work abbreviated as HA/SF) or HA-Tyr hydrogels. We demonstrated that all hydrogel formulations were cytocompatible and could promote the expression of cartilage matrix proteins allowing chondrocytes to produce ECM, while the most prominent chondrogenic effects were observed in hydrogels with HA20/SF80 polymeric ratios. Unconfined mechanical testing showed that the compressive modulus for HA20/SF80 chondrocyte-laden constructs was increased almost 10-fold over 28 days of culture in chondrogenic medium which confirmed the superior production of ECM in this hydrogel compared to other hydrogels in this study. Furthermore, in hydrogels loaded with anabolic and anti-inflammatory drugs, HA20/SF80 hydrogel showed the longest and the most sustained release profile over time which is desirable for the long treatment duration typically necessary for osteoarthritic joints. In conclusion, HA20/SF80 hydrogel was successfully established as a suitable injectable biomaterial for cartilage tissue engineering and drug delivery applications.

Nitrite-Responsive Hydrogel: Smart Drug Release Depending on the Severity of the Nitric Oxide-Related Disease.

Nitric oxide (NO) is known as one of the most important biomarkers of many diseases. However, the development of NO-triggered drug releasing platforms is challenging due to the low concentration and short lifetime of NO in vivo. In this work, a novel nitrite (NO2-)-responsive hydrogel (DHPL-GEL), which can be used for smart drug release depending on the severity of the NO-related disease, is demonstrated. A dihydropyridine cross-linking agent is designed to construct DHPL-GEL to enable the responsive degradation of the hydrogel triggered by NO2-. On-demand release of the drug loaded in DHPL-GEL was observed under the stimulation of various concentrations of NO2- at the physiological level both in vitro and in vivo. In the inflammatory arthritis rat model, the DHPL-GEL drug delivery system showed a better therapeutic effect and less side effects than the traditional therapy and nonresponsive hydrogel drug delivery system, demonstrating the promising application of the NO2--responsive hydrogel for the treatment of NO-related diseases.

Biodegradable double cross-linked chitosan hydrogels for drug delivery: Impact of chemistry on rheological and pharmacological performance

This study investigates the impact of dual ionic and covalent cross-links (ion-XrL and cov-XrL) on the properties of chitosan-based (CTS) hydrogels as eco-friendly drug delivery systems (DDS) for the model drug diclofenac sodium (DCNa). Citric acid and a diiodo-trehalose derivative (ITrh) were the chosen ionic and covalent cross-linker, respectively. The novel hydrogels completely disintegrated within 96 h by means of a hydrolysis process mediated by the enzyme trehalase. As far as the authors are aware, this is the first time that a trehalose derivative has been used as a covalent cross-linker in the formation of biodegradable hydrogels. The impact of CTS concentration and degree of cov-XrL on rheological parameters were examined by means of an experimental model design and marked differences were found between the materials. Hydrogels with maximum elastic properties were achieved at high CTS concentrations and high degrees of cov-XrL. DCNa-loaded formulations displayed well-controlled drug-release profiles strongly dependent on formulation composition (from 17% to 40% in 72 h). Surprisingly, higher degrees of covalent cross-linking led to a boost in drug release. The formulations presented herein provides a simple and straightforward pathway to design fully biodegradable, tailor-made controlled drug delivery systems with improved rheological properties.

Thermal sensitive Poloxamer/Chitosan hydrogel for drug delivery in vagina

In this paper, the composite gels based on poloxamer and chitosan with different contents were prepared for thermal sensitive mucosal drug delivery. The sol-gel transition temperature and rheological viscosity of the obtained gels were detected to select the optimum candidate for vaginal drug delivery. Electrochemistry impedance spectroscopy (EIS) was utilized to probe the hole structure in optimum hydrogel immersing in the vaginal fluid stimulant (VFS) for different time. The drug releasing rate of ethinyloestradiol loaded by the optimum hydrogel was examined. The drug releasing results suggested that the releasing rate satisfied with the Higuchi model, while the EIS results confirmed more pores in the composite gels would be formed during the immersing process in the VFS. The results indicated that the gel with the optimum formula met the requirements of vaginal medication. This research suggested poloxamer/chitosan might be an effective type of thermal gel for drug delivery in vagina.

Reversible Functionalization of Clickable Polyacrylamide Gels with Protein and Graft Copolymers.

Modular strategies to fabricate gels with tailorable chemical functionalities are relevant to applications spanning from biomedicine to analytical chemistry. Here, the properties of clickable poly(acrylamide-co-propargyl acrylate) (pAPA) hydrogels are modified via sequential in-gel copper-catalyzed azide-alkyne cycloaddition (CuAAC) reactions. Under optimized conditions, each in-gel CuAAC reaction proceeds with rate constants of ~0.003 s-1, ensuring uniform modifications for gels < 200 μm thick. Using the modular functionalization approach and a cleavable disulfide linker, pAPA gels were modified with benzophenone and acrylate groups. Benzophenone groups allow gel functionalization with unmodified proteins using photoactivation. Acrylate groups enabled copolymer grafting onto the gels. To release the functionalized unit, pAPA gels were treated with disulfide reducing agents, which triggered ~50 % release of immobilized protein and grafted copolymers. The molecular mass of grafted copolymers (~6.2 kDa) was estimated by monitoring the release process, expanding the tools available to characterize copolymers grafted onto hydrogels. Investigation of the efficiency of in-gel CuAAC reactions revealed limitations of the sequential modification approach, as well as guidelines to convert a pAPA gel with a single functional group into a gel with three distinct functionalities. Taken together, we see this modular framework to engineer multifunctional hydrogels as benefiting applications of hydrogels in drug delivery, tissue engineering, and separation science.

A novel Ag/AgO/carboxymethyl chitosan bacteriostatic hydrogel for drug delivery

pH-sensitive Ag/AgO/carboxymethyl chitosan (CMCS) bacteriostatic hydrogels and Ag/AgO/CMCS/Aspirin (ASP) carrier hydrogels were prepared by Ag/AgO in situ precipitation method, and the effects of swelling, degradation, drug release and antibacterial properties of hydrogels were studied. The network of Ag/AgO/CMCS/ASP drug-loaded gels produced was mainly cross-linking by hydrogen bonding and intermolecular forces, and the cross-linking silver was mainly present in the elemental Ag and Ag2+ states. Under the condition of buffer solution pH = 7.4, the cumulative release amount of Ag/AgO/CMCS/ASP drug-loaded gel was 75.20% within 12 h, and the inhibition rate of Gram-negative Escherichia coli (E. coli) reached the maximum of 92.32%, which had broad application prospects in the medical field.

Smart Supra- and Macro-Molecular Tools for Biomedical Applications.

Stimuli-responsive, “smart” polymeric materials used in the biomedical field function in a bio-mimicking manner by providing a non-linear response to triggers coming from a physiological microenvironment or other external source. They are built based on various chemical, physical, and biological tools that enable pH and/or temperature-stimulated changes in structural or physicochemical attributes, like shape, volume, solubility, supramolecular arrangement, and others. This review touches on some particular developments on the topic of stimuli-sensitive molecular tools for biomedical applications. Design and mechanistic details are provided concerning the smart synthetic instruments that are employed to prepare supra- and macro-molecular architectures with specific responses to external stimuli. Five major themes are approached: (i) temperature- and pH-responsive systems for controlled drug delivery; (ii) glycodynameric hydrogels for drug delivery; (iii) polymeric non-viral vectors for gene delivery; (iv) metallic nanoconjugates for biomedical applications; and, (v) smart organic tools for biomedical imaging.

Kinetics of the thermal response of poly(N-isopropylacrylamide co methacrylic acid) hydrogel microparticles under different environmental stimuli: A time-lapse NMR study

HypothesisHydrogels of N-isopropylacrylamide and methacrylic acid (P(NIPAm-co-MAA)) display pH sensitivity and complex positively charged molecules through carboxylate groups, while having a critical solution temperature at which they reduce in volume and dehydrate. We aimed to elucidate how the responsiveness of MAA to environmental changes alters PNIPAm hydrogels at the molecular level using nuclear magnetic resonance (NMR). Time-lapse NMR allows us to follow the evolution of NMR signal under a temperature stimulus, providing unique information on conformational freedom of the hydrogel polymers. ExperimentsWe used time-lapse NMR to follow the evolution of the NMR signal with time over a temperature change from 25 to 40°C and to study the swelling/deswelling kinetics of P(NIPAm-co-MAA) microgels at different pH values and ionic strengths, and in the presence of positively charged molecules complexing carboxylate groups. FindingsAt acid pH, hydrogel collapse is favored over neutral pH, and at basic pH the carboxylates remain steadily hydrated during temperature increase. Increasing ionic strength results in a faster, more effective collapse than decreasing pH. Complexation of medium-sized molecules with several charges (spermine, spermidine) causes a faster collapse than complexation with large molecular weight poly(allylamine) hydrochloride, but similar to the collapse effected by large poly(diallyldimethylammonium) chloride. This work opens new perspectives to using time-lapse NMR to study thermoresponsive systems that respond to multiple stimuli, with particular relevance in designing hydrogels for drug delivery.

Technologies and Formulation Design of Polysaccharide-Based Hydrogels for Drug Delivery.

Polysaccharide-based hydrogel particles (PbHPs) are very promising carriers aiming to control and target the release of drugs with different physico-chemical properties. Such delivery systems can offer benefits through the proper encapsulation of many drugs (non-steroidal and steroidal anti-inflammatory drugs, antibiotics, etc) ensuring their proper release and targeting. This review discusses the different phases involved in the production of PbHPs in pharmaceutical technology, such as droplet formation (SOL phase), sol-gel transition of the droplets (GEL phase) and drying, as well as the different methods available for droplet production with a special focus on prilling technique. In addition, an overview of the various droplet gelation methods with particular emphasis on ionic cross-linking of several polysaccharides enabling the formation of particles with inner highly porous network or nanofibrillar structure is given. Moreover, a detailed survey of the different inner texture, in xerogels, cryogels or aerogels, each with specific arrangement and properties, which can be obtained with different drying methods, is presented. Various case studies are reported to highlight the most appropriate application of such systems in pharmaceutical field. We also describe the challenges to be faced for the breakthrough towards clinic studies and, finally, the market, focusing on the useful approach of safety-by-design (SbD).

Electrodeposition of Polysaccharide and Protein Hydrogels for Biomedical Applications.

In the last few decades, polysaccharide and protein hydrogels have attracted significant attentions and been applied in various engineering fields. Polysaccharide and protein hydrogels with appealing physical and biological features have been produced to meet different biomedical applications for their excellent properties related to biodegradability, biocompatibility, nontoxicity, and stimuli responsiveness. Numerous methods, such as chemical crosslinking, photo crosslinking, graft polymerization, hydrophobic interaction, polyelectrolyte complexation and electrodeposition have been employed to prepare polysaccharide and protein hydrogels. Electrodeposition is a facile way to produce different polysaccharide and protein hydrogels with the advantages of temporal and spatial controllability. This paper reviews the recent progress in the electrodeposition of different polysaccharide and protein hydrogels. The strategies of pH induced assembly, Ca2+ crosslinking, metal ions induced assembly, oxidation induced assembly derived from electrochemical methods were discussed. Pure, binary blend and ternary blend polysaccharide and protein hydrogels with multiple functionalities prepared by electrodeposition were summarized. In addition, we have reviewed the applications of these hydrogels in drug delivery, tissue engineering and wound dressing.

Locally Controlled Release of Methotrexate and Alendronate by Thermo-Sensitive Hydrogels for Synergistic Inhibition of Osteosarcoma Progression.

Osteosarcoma (OS) is a serious primary bone malignant tumor that can easily affect children and adolescents. Chemotherapy is one of the important and feasible clinical treatment strategies for the treatment of OS at present, which is severely limited due to insufficient retention time, poor penetration ability, and serious side effects of current anti-tumor drug preparations. In this work, a novel injectable thermo-sensitive hydrogel (mPEG45–PLV19) loaded with methotrexate and alendronate, and the sustained release at the tumor site synergistically inhibited the progression of OS. The mPEG45–PLV19 shows excellent physical and chemical properties. Compared with other treatment groups, the in vivo treatment of gel+ methotrexate + alendronate effectively inhibited the growth of tumor. More importantly, it significantly reduced bone destruction and lung metastasis caused by OS. Therefore, this injectable thermo-sensitive hydrogel drug delivery system has broad prospects for OS chemotherapy.

2-Thiobarbituric acid addition improves structural integrity and controlled drug delivery of biocompatible pectin hydrogels

Thiolated polymers are commonly preferred for biomedical applications with their good permeation properties providing them higher bioavailability. However, the thiolation process is mostly time-consuming series of chemical reactions. This study describes a simple irreversible thiol group integration to the pectin hydrogels by noncovalent bonding. We used 2-thiobarbituric acid (TBA) for thiolation. We proved with full-atom molecular dynamics simulations and experimental methods that TBA desertion is negligible. Pectin hydrogels become more flexible and their disintegration is delayed from 4 h up to four days with TBA addition. Also, hydrogels can successfully deliver the model drug, theophylline, showing a controlled release profile.

Advanced Hydrogels Based Drug Delivery Systems for Ophthalmic Delivery.

Hydrogels are aqueous gels composed of cross-linked networks of hydrophilic polymers. Stimuli-responsive based hydrogels have gained focus over the past 20 years for treating ophthalmic diseases. Different stimuli-responsive mechanisms are involved in forming polymer hydrogel networks, including change in temperature, pH, ions, and others including light, thrombin, pressure, antigen, and glucose-responsive. Incorporation of nanocarriers with these smart stimuli-responsive drug delivery systems that can extend the duration of action by increasing ocular bioavailability and reducing the dosing frequency. This review will focus on the hydrogel drug delivery systems highlighting the gelling mechanisms and emerging stimuli-responsive hydrogels from preformed gels, nanogels, and the role of advanced 3D printed hydrogels in vision-threatening diseases like age-related macular degeneration and retinitis pigmentosa. It also provides insight into the limitations of hydrogels along with the safety and biocompatibility of the hydrogel drug delivery systems.