title: The potential application of hyaluronic acid coated chitosan nanoparticles in ocular delivery of dexamethasone.
abstract: This study investigates in-vitro transcorneal permeation on excised-rabbit cornea and its effect on corneal hydration-level, in-vivo ocular irritation, tear and aqueous humor dexamethasone-sodium-phosphate (DEX) concentration after topical administration of chitosan-nanoparticles (CS-NPs), hyaluronan-coated-CS-NPs (HA-CS-NPs) and DEX-aqueous-solution in rabbit eyes. The permeation parameters and irritation results indicated the ocular safety of NPs. The developed UPLC-method was successfully applied for DEX quantification in tears and aqueous-humors. Tear samples were collected and DEX-concentration was analyzed by UPLC. A statistically significantly (p<0.05) high DEX-concentration in the inferior conjunctival-sulcus from NPs treated eyes was found as compared to DEX-solution treated eyes. Similarly, DEX-concentration in aqueous-humor was estimated. The drug was detected sufficiently high in aqueous-humor till 24h following topical administration of NPs. The NPs have shown significantly (p<0.05) higher bioavailability of DEX compared to DEX-solution. About 1.83- and 2.14-fold higher AUC0-24h was observed with the CS-NPs and HA-CS-NPs, respectively compared to DEX-solution. The reason for higher tear concentration and higher bioavailability of DEX from uncoated and HA-coated CS-NPs was assumed due to their prolonged precorneal-retention because of highly mucoadhesive characteristics of CS and HA. Moreover, presence of HA on CS-NPs, speed-up cellular-uptake by receptor-mediated-endocytosis could be another reason for enhanced bioavailability.
authors.affiliation: Nanomedicine Research Unit, Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box: 2457, Riyadh 11451, Saudi Arabia. Electronic address: makalam@ksu.edu.sa.
authors.forename: Mohd Abul
authors.initials: MA
authors.lastname: Kalam
mesh_terms: D000287:Administration, Topical; D000818:Animals; D048271:Chitosan / Q000008:administration & dosage* / Q000737:chemistry; D003315:Cornea / Q000187:drug effects / Q000473:pathology; D003907:Dexamethasone / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry / Q000627:therapeutic use; D016503:Drug Delivery Systems; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009883:Ophthalmic Solutions / Q000737:chemistry / Q000627:therapeutic use; D011817:Rabbits
chemical_list: D004337:Drug Carriers; D009883:Ophthalmic Solutions; D003907:Dexamethasone; D048271:Chitosan
keywords: Aqueous-humor; Chitosan-nanoparticles; Dexamethasone; Ocular irritation; Tear-fluid; Transcorneal permeation