Bimatoprost-loaded ocular inserts as sustained release drug delivery systems for glaucoma treatment: in vitro and in vivo evaluation

Autor: Renata Bravo, Simone Odília Antunes Fernandes, Leonardo Lima Fuscaldi, Juçara R. Franca, Sebastião Cronemberger, Rachel Oliveira Castilho, Anderson J. Ferreira, Valbert Nascimento Cardoso, Lívia B Rodrigues, Tatiana G. Ribeiro, André Augusto Gomes Faraco, Giselle Foureaux, Maria Irene Yoshida
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Male
Intraocular pressure
Eye Diseases
genetic structures
medicine.medical_treatment
Glaucoma
Ocular hypertension
lcsh:Medicine
Administration
Ophthalmic
Drug Delivery Systems
Spectroscopy
Fourier Transform Infrared
Medicine and Health Sciences
Tissue Distribution
lcsh:Science
Mammals
Drug Distribution
Multidisciplinary
Calorimetry
Differential Scanning
Cloprostenol
Animal Models
Vertebrates
Physical Sciences
Drug delivery
Materials Characterization
Research Article
Biotechnology
medicine.drug
medicine.medical_specialty
Drug Research and Development
Materials Science
In Vitro Techniques
Research and Analysis Methods
Rodents
Retinal ganglion
Biomaterials
Natural Materials
Model Organisms
In vivo
Ophthalmology
medicine
Animals
Humans
Pharmacokinetics
Rats
Wistar
Intraocular Pressure
Pharmacology
Bimatoprost
business.industry
lcsh:R
Organisms
Biology and Life Sciences
Eye drop
medicine.disease
Amides
eye diseases
Rats
Surgery
Drug Liberation
Delayed-Action Preparations
Microscopy
Electron
Scanning
lcsh:Q
sense organs
Clinical Medicine
business
Zdroj: PLoS ONE, Vol 9, Iss 4, p e95461 (2014)
PLoS ONE
ISSN: 1932-6203
Popis: The purpose of the present study was to develop and assess a novel sustained-release drug delivery system of Bimatoprost (BIM). Chitosan polymeric inserts were prepared using the solvent casting method and characterized by swelling studies, infrared spectroscopy, differential scanning calorimetry, drug content, scanning electron microscopy and in vitro drug release. Biodistribution of 99mTc-BIM eye drops and 99mTc-BIM-loaded inserts, after ocular administration in Wistar rats, was accessed by ex vivo radiation counting. The inserts were evaluated for their therapeutic efficacy in glaucomatous Wistar rats. Glaucoma was induced by weekly intracameral injection of hyaluronic acid. BIM-loaded inserts (equivalent to 9.0 µg BIM) were administered once into conjunctival sac, after ocular hypertension confirmation. BIM eye drop was topically instilled in a second group of glaucomatous rats for 15 days days, while placebo inserts were administered once in a third group. An untreated glaucomatous group was used as control. Intraocular pressure (IOP) was monitored for four consecutive weeks after treatment began. At the end of the experiment, retinal ganglion cells and optic nerve head cupping were evaluated in the histological eye sections. Characterization results revealed that the drug physically interacted, but did not chemically react with the polymeric matrix. Inserts sustainedly released BIM in vitro during 8 hours. Biodistribution studies showed that the amount of 99mTc-BIM that remained in the eye was significantly lower after eye drop instillation than after chitosan insert implantation. BIM-loaded inserts lowered IOP for 4 weeks, after one application, while IOP values remained significantly high for the placebo and untreated groups. Eye drops were only effective during the daily treatment period. IOP results were reflected in RGC counting and optic nerve head cupping damage. BIM-loaded inserts provided sustained release of BIM and seem to be a promising system for glaucoma management.
Databáze: OpenAIRE
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