Chitosan-Based In Situ Gels for Ocular Delivery of Therapeutics: A State-of-the-Art Review

Abstract

Ocular in situ gels are a promising alternative to overcome drawbacks of conventional eye drops because they associate the advantages of solutions such as accuracy and reproducibility of dosing, or ease of administration with prolonged contact time of ointments. Chitosan is a natural polymer suitable for use in ophthalmic formulations due to its biocompatibility, biodegradability, mucoadhesive character, antibacterial and antifungal properties, permeation enhancement and corneal wound healing effects. The combination of chitosan, pH-sensitive polymer, with other stimuli-responsive polymers leads to increased mechanical strength of formulations and an improved therapeutic effect due to prolonged ocular contact time. This review describes in situ gelling systems resulting from the association of chitosan with various stimuli-responsive polymers with emphasis on the mechanism of gel formation and application in ophthalmology. It also comprises the main techniques for evaluation of chitosan in situ gels, along with requirements of safety and ocular tolerability.

Progress in the Development of Chitosan-Based Biomaterials for Tissue Engineering and Regenerative Medicine

“…However, low solubility under physiological pH possesses some limitations. Due to its mucoadhesive nature [101], CS has been used as a vehicle to deliver drugs to nasal [102], ocular [103], buccal [104], and pulmonary tissues [105]. For drug delivery purposes, CS is used in the form of nano/microparticles which is synthesized by emulsion, coacervation/precipitation, ionic gelation, reverse micellar methods, etc.…”

In vitro–in vivo evaluation of tetrahydrozoline‐loaded ocular in situ gels on rabbits for allergic conjunctivitis management

“…In situ activated gel‐forming systems can be described as viscous liquids which by changing physiological conditions (pH, temperature, ionic strength, and UV) will shift to a gel phase (Venkatesh, Liladhar, Kumar, & Shivakumar, 2011). Situ gels, which can undergo gelation due to physiological conditions exposure such as temperature or pH, could be of the most ideal formulations for various diseases (Irimia et al, 2018). A variety of synthetic or natural macromolecules are applied to form in situ gels (Üstündağ Okur et al, 2019).…”

Chitosan and its Derivatives for Ocular Delivery Formulations: Recent Advances and Developments

“…Numerous polymers are extensively used for hydrogel preparation in pharmaceutical technology, as well as for ocular drug release, including natural polymers such as polysaccharides, gellan, ALG, HPMC, carrageenans, CS, and their derivatives, as well as some synthetic polymers, such as poloxamers and polyacrylates [41,228,229]. Blends between them can be used also as hydrogels for drug delivery in ophthalmic applications [230].…”