Mucoadhesive cholesterol-chitosan self-assembled particles for topical ocular delivery of dexamethasone

Natallia V Dubashynskaya; Alexey S Golovkin; Igor V Kudryavtsev; Stanislava S Prikhodko; Andrey S Trulioff; Anton N Bokatyi; Daria N Poshina; Sergei V Raik; Yury A Skorik

doi:10.1016/j.ijbiomac.2020.04.251

Mucoadhesive cholesterol-chitosan self-assembled particles for topical ocular delivery of dexamethasone

Int J Biol Macromol. 2020 May 1:158:811-818. doi: 10.1016/j.ijbiomac.2020.04.251. Online ahead of print.

Authors

Natallia V Dubashynskaya¹, Alexey S Golovkin², Igor V Kudryavtsev³, Stanislava S Prikhodko², Andrey S Trulioff⁴, Anton N Bokatyi¹, Daria N Poshina¹, Sergei V Raik⁵, Yury A Skorik⁶

Affiliations

¹ Institute of Macromolecular Compounds of the Russian Academy of Sciences, Bolshoy pr. V.O. 31, St. Petersburg 199004, Russian Federation.
² Almazov National Medical Research Centre, Akkuratova st. 2, St. Petersburg 197341, Russian Federation.
³ Institute of Experimental Medicine, Akademika Pavlova st. 12, St. Petersburg 197376, Russian Federation; Far Eastern Federal University, Sukhanova st. 8, Vladivostok 690090, Russian Federation.
⁴ Institute of Experimental Medicine, Akademika Pavlova st. 12, St. Petersburg 197376, Russian Federation.
⁵ Institute of Macromolecular Compounds of the Russian Academy of Sciences, Bolshoy pr. V.O. 31, St. Petersburg 199004, Russian Federation; Institute of Chemistry, St. Petersburg State University, Universitetskii pr. 26, Peterhof, St. Petersburg 198504, Russian Federation.
⁶ Institute of Macromolecular Compounds of the Russian Academy of Sciences, Bolshoy pr. V.O. 31, St. Petersburg 199004, Russian Federation; Institute of Chemistry, St. Petersburg State University, Universitetskii pr. 26, Peterhof, St. Petersburg 198504, Russian Federation. Electronic address: yury_skorik@mail.ru.

PMID: 32371131
DOI: 10.1016/j.ijbiomac.2020.04.251

Abstract

The topical application of ophthalmic drugs is a convenient and safe mode of drug administration. However, the bioavailability of topical drugs in the eye is low due to eye barriers and the rapid removal of the drug from the conjunctival surface by the tear fluid. The aim of this study was to obtain dexamethasone-loaded mucoadhesive self-assembled particles based on a conjugate of succinyl cholesterol with chitosan (SC-CS) for potential use as a topical ocular formulation. SC-CS was obtained via a carbodiimide-mediated coupling reaction (degree of substitution DS 1.2-5.8%). SC-CS in the DS range of 1.2-3.0% can self-organize in solution to form positively charged particles (ζ-potential 20-37 mV) of submicron size (hydrodynamic diameter 700-900 nm). The SC-CS particles show good mucoadhesiveness, which decreases with increasing DS. The obtained particles can encapsulate 159-170 μg/mg dexamethasone; they release about 50% of drug in 2 h, and the cumulative drug release reached 95% in 24 h. A cell model confirmed that dexamethasone-loaded SC-CS particles are non-cytotoxic and exhibit a comparable anti-inflammatory activity to that of pure dexamethasone. Testing the osmotic resistance of erythrocytes showed that both dexamethasone-loaded and non-loaded SC-CS particles have greater membrane-stabilizing ability than that of dexamethasone.

Keywords: Anti-inflammatory activity; Cholesterol-chitosan; Dexamethasone; Mucoadhesion; Ocular drug delivery; Self-assembled particles.