Current Pharmaceutical Design - Volume 29, Issue 40, 2023

Hydrogels are a three-dimensional (3D) network of hydrophilic polymers. The physical and chemical crosslinking of polymeric chains maintains the structure of the hydrogels even when they are swollen in water. They can be modified with thiol by thiol epoxy, thiol-ene, thiol-disulfide, or thiol-one reactions. Their application as a matrix for protein and drug delivery, cellular immobilization, regenerative medicine, and scaffolds for tissue engineering was initiated in the early 21st century. This review focuses on the ingredients, classification techniques, and applications of hydrogels, types of thiolation by different thiol-reducing agents, along with their mechanisms. In this study, different applications for polymers used in thiolated hydrogels, including dextran, gelatin, polyethylene glycol (PEG), cyclodextrins, chitosan, hyaluronic acid, alginate, poloxamer, polygalacturonic acid, pectin, carrageenan gum, arabinoxylan, carboxymethyl cellulose (CMC), gellan gum, and polyvinyl alcohol (PVA) are reviewed.

The physicochemical properties of polymeric hydrogels render them attractive for the development of 3D printed prototypes for tissue engineering in regenerative medicine. Significant effort has been made to design hydrogels with desirable attributes that facilitate 3D printability. In addition, there is significant interest in exploring stimuli-responsive hydrogels to support automated 3D printing into more structurally organised prototypes such as customizable bio-scaffolds for regenerative medicine applications. Synthesizing stimuli-responsive hydrogels is dependent on the type of design and modulation of various polymeric materials to open novel opportunities for applications in biomedicine and bio-engineering. In this review, the salient advances made in the design of stimuli-responsive polymeric hydrogels for 3D printing in tissue engineering are discussed with a specific focus on the different methods of manipulation to develop 3D printed stimuli-responsive polymeric hydrogels. Polymeric functionalisation, nano-enabling and crosslinking are amongst the most common manipulative attributes that affect the assembly and structure of 3D printed bio-scaffolds and their stimuli- responsiveness. The review also provides a concise incursion into the various applications of stimuli to enhance the automated production of structurally organized 3D printed medical prototypes.

Liposomes have gained a lot of interest for drug delivery applications, and some of these preparations have been commercialized. These are formulated with biocompatible components and can be used for delivering a wide range of payloads differing in aqueous solubility and molecular weight. Liposome-based delivery approaches are limited mainly by two factors: (a) poor dispersion stability, and (b) pre-mature leakage of payloads. In this review, we have discussed the stabilization of liposomal vesicles by their entrapment in hydrogels. Studies reveal that such hydrogels can maintain the structural integrity of liposomes. Release of liposomes from the hydrogel network can be modulated through careful screening of matrix former and degree of its cross-linking. Accordingly, we have reviewed the approaches of stabilizing liposomal vesicles through entrapment in hydrogels. Application of liposome-embedded hydrogels has been reviewed in context of localized drug delivery. Our discussion is focussed on the delivery of bioactives to the skin. Such an approach appears alluring from the standpoint of minimizing the undesirable distribution of payload(s) the systemic circulation and off-target sites.

Infected wounds that do not heal are a worldwide problem that is worsening, with more people dying and more money being spent on care. For any disease to be managed effectively, its root cause must be addressed. Effective wound care becomes a bigger problem when various traditional wound healing methods and products may not only fail to promote good healing. Still, it may also hinder the healing process, causing wounds to stay open longer. Progress in tissue regeneration has led to developing three-dimensional scaffolds (3D) or constructs that can be leveraged to facilitate cell growth and regeneration while preventing infection and accelerating wound healing. Tissue regeneration uses natural and fabricated biomaterials that encourage the growth of tissues or organs. Even though the clinical need is urgent, the demand for polymer-based therapeutic techniques for skin tissue abnormalities has grown quickly. Hydrogel scaffolds have become one of the most imperative 3D cross-linked scaffolds for tissue regeneration because they can hold water perfectly and are porous, biocompatible, biodegradable, and biomimetic. For damaged organs or tissues to heal well, the porosity topography of the natural extracellular matrix (ECM) should be imitated. This review details the scaffolds that heal wounds and helps skin tissue to develop. After a brief overview of the bioactive and drug-loaded polymeric hydrogels, the discussion moves on to how the scaffolds are made and what they are made of. It highlights the present uses of in vitro and in-vivo employed biomimetic scaffolds. The prospects of how well bioactiveloaded hydrogels heal wounds and how nanotechnology assists in healing and regeneration have been discussed.

The blood-brain barrier (BBB) regulates blood and chemical exchange in the central nervous system. It is made up of brain parenchyma capillary endothelial cells. It separates the interstitial cerebrospinal fluid from the circulation and limits brain drug entry. Peptides, antibodies, and even tiny hydrophilic biomolecules cannot flow across the BBB due to their semi-permeability. It protects the brain from poisons, chemicals, and pathogens, and blood cells penetrate brain tissue. BBB-facilitated carrier molecules allow selective permeability of nutrients such as D-glucose, L-lactic acid, L-phenylalanine, L-arginine, and hormones, especially steroid hormones. Brain barriers prevent drug molecules from entering, making medication delivery difficult. Drugs can reach specific brain regions through the nasal cavity, making it a preferred route. The in-situ gels are mucoadhesive, which extends their stay in the nasal cavity, allows them to penetrate deep and makes them a dependable way of transporting numerous medications, including peptides and proteins, straight into the central nervous system. This approach holds great potential for neurological therapy as they deliver drugs directly to the central nervous system, with less interference and better drug release control. The brain affects daily life by processing sensory stimuli, controlling movement and behaviour, and sustaining mental, emotional, and cognitive functioning. Unlike systemic routes, the nasal mucosa is extensively vascularized and directly contacts olfactory sensory neurons. Compared to the systemic circulation, this improves brain bioavailability of medications. Drugs can be delivered to the brain using in-situ gel formulations safely and efficiently, with a greater therapeutic impact than with traditional techniques.

The prevalence of vaginal infection is increasing among women, especially at reproductive age. For proper eradication of infection, the effective concentration of a drug is required at the infection site. Therefore, local delivery is recommended to exert a direct therapeutic effect at the site action that causes a reduction in dose and side effects. The main focus of vaginal drug delivery is to enhance retention time and patient compliance. The high recurrence rate of vaginal infection due to the lack of effective treatment strategies opens the door for new therapeutic approaches. To combat these setbacks, intravaginal gene therapies have been investigated. High attention has been gained by vaginal gene therapy, especially for sexually transmitted infection treatment. Despite much research, no product is available in the market, although in vitro and preclinical data support the vaginal route as an effective route for gene administration. The main focus of this review is to discuss the recent advancement in miniaturized polymeric systems for intravaginal gene therapies to treat local infections. An overview of different barriers to vaginal delivery and challenges of vaginal infection treatment are also summarised.