Bimatoprost-loaded ocular inserts as sustained release drug delivery systems for glaucoma treatment: in vitro and in vivo evaluation.
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.
Department of Pharmaceutical Products, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Juçara Ribeiro
JR
Franca
Department of Morphology, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Giselle
G
Foureaux
Department of Clinical and Toxicological Analysis, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Leonardo Lima
LL
Fuscaldi
Department of Pharmaceutical Products, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Tatiana Gomes
TG
Ribeiro
Department of Pharmaceutical Products, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Lívia Bomfim
LB
Rodrigues
Department of Pharmaceutical Products, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Renata
R
Bravo
Department of Pharmaceutical Products, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Rachel Oliveira
RO
Castilho
Department of Chemistry, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Maria Irene
MI
Yoshida
Department of Clinical and Toxicological Analysis, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Valbert Nascimento
VN
Cardoso
Department of Clinical and Toxicological Analysis, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Simone Odília
SO
Fernandes
Department of Ophthalmology and Otolaryngology, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Sebastião
S
Cronemberger
Department of Morphology, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Anderson José
AJ
Ferreira
Department of Pharmaceutical Products, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
André Augusto Gomes
AA
Faraco
D060433:Administration, Ophthalmic; D000577:Amides / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000818:Animals; D000069580:Bimatoprost; D002152:Calorimetry, Differential Scanning; D003008:Cloprostenol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D005901:Glaucoma / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D066298:In Vitro Techniques; D007429:Intraocular Pressure; D008297:Male; D008855:Microscopy, Electron, Scanning; D051381:Rats; D017208:Rats, Wistar; D017550:Spectroscopy, Fourier Transform Infrared; D014018:Tissue Distribution
D000577:Amides; D003692:Delayed-Action Preparations; D003008:Cloprostenol; D000069580:Bimatoprost