Journal
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
Volume 89, Issue -, Pages 559-568Publisher
ELSEVIER
DOI: 10.1016/j.ijbiomac.2016.05.016
Keywords
Chitosan-nanoparticles; Dexamethasone; Transcorneal permeation; Ocular irritation; Tear-fluid; Aqueous-humor
Funding
- College of Pharmacy Research Center at King Saud University
- Deanship of Scientific Research at King Saud University
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This study investigates in-vitro trans corneal 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 AUC(0-24h) 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. (C) 2016 Elsevier B.V. All rights reserved.
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