Spatio-temporal control on the delivery of triamcinolone acetonide using polymeric nanoparticles reduces steroid induced cataract

[Display omitted] Development of topically administered drug delivery systems for the treatment of ocular diseases have majorly focused on enhancing bioavailability of drugs in the ocular tissues. However, control of spatial distribution of topically administered drugs so as to restrict/avoid drug b...

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Bibliographic Details
Published in:International journal of pharmaceutics 2019-09, Vol.568, p.118474-118474, Article 118474
Main Authors: Srinivasarao, Dadi A., Reddy, S. Sreenivasa, Reddy, G. Bhanuprakash, Katti, Dhirendra S.
Format: Article
Language:English
Subjects:
Administration, Ophthalmic
Animals
Biological Availability
Cadherins - metabolism
Cataract - chemically induced
Cataract - drug therapy
Cataract - metabolism
Cataract - pathology
Coumarins - administration & dosage
Coumarins - chemistry
Coumarins - pharmacokinetics
Diabetes Mellitus, Experimental - drug therapy
Diabetes Mellitus, Experimental - metabolism
Diabetes Mellitus, Experimental - pathology
Drug Delivery Systems
Drug Liberation
Eye
Eye - drug effects
Eye - metabolism
Eye - pathology
Glucocorticoids - administration & dosage
Glucocorticoids - chemistry
Lens
Male
Mice, Inbred C57BL
Ocular biodistribution
PCL-PF68 core-shell nanoparticles
Poloxamer - administration & dosage
Poloxamer - chemistry
Polyesters - administration & dosage
Polyesters - chemistry
Posterior subcapsular cataract
Rats, Sprague-Dawley
Thiazoles - administration & dosage
Thiazoles - chemistry
Thiazoles - pharmacokinetics
Triamcinolone acetonide
Triamcinolone Acetonide - administration & dosage
Triamcinolone Acetonide - chemistry
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Summary:[Display omitted] Development of topically administered drug delivery systems for the treatment of ocular diseases have majorly focused on enhancing bioavailability of drugs in the ocular tissues. However, control of spatial distribution of topically administered drugs so as to restrict/avoid drug bioavailability at sensitive ocular tissues that are prone to drug induced adverse effects has not been explored. In this study, we aimed to reduce the bioavailability of topically administered corticosteroid, triamcinolone acetonide (TA) in lens via controlled spatial distribution in order to minimize TA induced posterior subcapsular cataract (PSC). For this, a negatively charged polymeric core-shell nanoparticulate drug delivery system composed of polycaprolactone (PCL) core and pluronic® F-68 (PF68) shell was fabricated. For in vivo studies, coumarin-6 (COU) loaded nanoparticles (NPs) were fabricated and studied for their biodistribution after topical administration in mice eyes and compared with free COU biodistribution. The administered COU loaded NPs differentially distributed in mice eyes and showed lower bioavailability in lens compared to free COU. Further, in vivo efficacy of the delivery system for its ability to minimize the rate of PSC progression was evaluated in diabetic rats. The results demonstrated that TA loaded PCL-PF68 NPs decreased PSC progression compared to free TA when administered topically.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2019.118474