Potential of Stimuli-Responsive In Situ Gel System for Sustained Ocular Drug Delivery: Recent Progress and Contemporary Research

Abstract

Eyesight is one of the most well-deserved blessings, amid all the five senses in the human body. It captures the raw signals from the outside world to create detailed visual images, granting the ability to witness and gain knowledge about the world. Eyes are exposed directly to the external environment; they are susceptible to the vicissitudes of diseases. The World Health Organization has predicted that the number of individuals affected by eye diseases will rise enormously in the next decades. However, the physical barriers of the eyes and the problems associated with conventional ocular formulations are significant challenges in ophthalmic drug development. This has generated the demand for a sustained ocular drug delivery system, which serves to deliver effective drug concentration at a reduced frequency for consistent therapeutic effect and better patient treatment adherence. Recent advancement in pharmaceutical dosage design has demonstrated that a stimuli-responsive in situ gel system exhibits the favorable characteristics for providing sustained ocular drug delivery and enhanced ocular bioavailability. Stimuli-responsive in situ gels undergo a phase transition (solution–gelation) in response to the ocular environmental temperature, pH, and ions. These stimuli transform the formulation into a gel at the cul de sac to overcome the shortcomings of conventional eye drops, such as rapid nasolacrimal drainage and short contact time with the ocular surface This review highlights the recent successful research outcomes of stimuli-responsive in situ gelling systems in treating in vivo models with glaucoma and various ocular infections. Additionally, it also presents the mechanism, recent development, and safety considerations of stimuli-sensitive in situ gel as the potential sustained ocular delivery system for treating common eye disorders.

Response Surface Methodology for Optimization of Buspirone Hydrochloride-Loaded In Situ Gel for Pediatric Anxiety

“…From the obtained data, it was concluded that the relative bioavailability of the BH-loaded in situ gel was higher than the drug solution by more than 1.5-fold. The enhanced relative bioavailability of the BH may have been due to the decreased release of the drug from the in situ gel, which led to a more sustained release and absorption of the drug compared to the free-solution form [ 15 , 24 ].…”

Advances and Challenges in Intranasal Delivery of Antipsychotic Agents Targeting the Central Nervous System

“…Gels are semisolid dosage forms with three-dimensional polymeric matrices comprising a small amount of solids carrying a large amount of liquid ( Pandey et al, 2021 ). The in situ gelling system has the capability to convert from sol-to-gel upon application to the site of administration.…”

Cellulosic Polymers for Enhancing Drug Bioavailability in Ocular Drug Delivery Systems

“…These polymers cause a slower elimination of the drug; examples are cellulose derivatives such as protein (collagen, silk, gelatin), polysaccharide (chitosan, starch, alginate), polyesters (polycaprolactone, polylactide, polylactide/polyglycolic copolymer) [35], and cellulose derivatives such as HPMC [77], hydroxyethyl cellulose [78], and methylcellulose. In situ gels are delivered as a solution or suspension and rapidly undergoes sol-gel transition [79] upon external stimuli such pH, temperature, and ionic strength [80]. This has merits such as reproducible and accurate dosing.…”