Penetration Enhancers and Ocular Bioadhesives: Two New Avenues for Ophthalmic Drug Delivery

Abstract

This review is focused on the two avenues of development that promise a major impact on future ocular drug therapeutics: bioadhesives, including hydrogels and other agents like carbopols, polyacrylic acids, chitosan, etc., and penetration enhancers, including different surfactants, calcium chelators, etc. The capacity of some polymers to adhere to the mucin coat covering the conjunctiva and the corneal surface of the eye forms the basis for ocular mucoadhesion. These systems markedly prolong the residence time of a drug in the conjunctival sac, since clearence is now controlled by the much slower rate of mucus turnover rather than the tear turnover rate. But improving the corneal drug retention alone is inadequate in bringing about a significant improvement of drug bioavailability. Another approach consists of transiently increasing the pentration characteristics of the cornea with appropriate substances, known as penetration enhancers or absorption promoters. The main aim of this article is to give an insight into the potential application of mucoadhesives and corneal penetration enhancers for the conception of innovative opthalmic delivery appraoches, to decrease the systemic side effects, and create a more focused effect, which may be achieved with lower doses of the drug. Ophthalmic formulations based on these mucoadhesives and penetration enhancers are simple to manufacture and exhibit an excellent tolerance when administered into the cornea. The use of the former considerably prolongs the corneal contact time and the use of the latter increases the rate and amount of drug transport. The various corneal epithelial barriers along with the major routes of transport of drugs are discussed. The article includes a list of the various substances in use or under investigation for the aforementioned properties, along with their mechanisms of action. A fair appraisal of the subject with regard to these two therapeutic approaches and any expected ill effects has been made.

Ciprofloxacin as Ocular Liposomal Hydrogel

“…Other mechanisms such as endocytosis of liposomes or fusion of liposome membrane with the plasmalemma are also involved in enhanced transport (43). While liposomal hydrogel show 5-folds higher permeation than aqueous solution, this may explained by the fact that mucoadhesive properties of hydrogel base ensures an intimate contact between liposomes and corneal membrane which prolong the retention of the formulation at the site of administration, which is beneficial for enhancing permeation (44,45). …”

Formulation and corneal permeation of ketorolac tromethamine-loaded chitosan nanoparticles

“…There have been studies over the years examining the mechanism of drug release and reporting on ocular therapeutic efficacy of drugs delivered using nanoparticles (Zhu et al, 2012). Furthermore, such drug delivery systems are advocated as an ophthalmic drug delivery systems that may enhance dosage form acceptability while providing sustained release action (Kaur & Smitha, 2002).…”

Quitosana: biopolímero funcional com potencial industrial biomédico

“…71,81 A quitosana exibe comportamento biológico favorável, tais como bioadesão, permeabilidade e características fisico-químicas interessantes, que tornam este biopolímero um material único para design de sistemas de liberação de fármaco ocular. [82][83][84][85] A quitosana é considerada um bom sistema de liberação de fármacos na cavidade bucal, visto que a sua atividade antibacteriana pode ser devida às interações eletrostáticas entre grupos amino e grupos aniônicos nas paredes celulares das bactérias provenientes de resíduos de ácidos carboxílicos e fosfolipídeos. 86 Sistemas de liberação bucal mucoadesivos desenvolvidos por hidrogéis de quitosana parecem ser apropriados para prolongar o tempo de residência da forma farmacêutica, melhorando o efeito terapêutico no tratamento de infecções localizadas, tais como doença periodontal e estomatite.…”