Bakteriyel Keratit Tedavisine Yönelik Besifloksasin Yüklü Oküler İnsertlerin Elektro-Eğirme Yöntemi ile Geliştirilmesi ve Değerlendirilmesi

Abstract

Polat, H.K. Development and Evaluation of Besifloxacin HCl Loaded Ocular Inserts by Electro-Spinning Method for Bacterial Keratitis Treatment, Hacettepe University Graduate School of Health Sciences, Pharmaceutical Technology Programme, Ph.D Thesis, Ankara, 2020. Bacterial keratitis is a disease characterized by inflammation caused by different pathogens in the eye and in cases where treatment does not occur, can cause serious vision loss and even blindness. In this thesis, nanofibrous insert formulation groups containing besifloxacin HCl (BH) were evaluated in vitro, ex vivo and in vivo as a potential ocular drug delivery system for the treatment of bacterial keratitis. Insert formulations containing BH were prepared by electro-spinning method using Poly (caprolactone) / polyethylene glycol (PKL / PEG) polymer. The inserts were coated with sodium alginate (SA) or thiolated sodium alginate (TSA) to provide the formulations mucoadhesive properties. In order to take advantage of the cyclodextrin (Cyc)’s ocular penetration enhancing properties, BH-Cyc complex was used instead of BH in a group of formulations. In in vitro drug release studies, it was determined that inserts in the nanofiber structure show a burst release within the first two days and then a slow release profile. Coating the insert surfaces with SA and TSA has been found to increase the bioadhesion properties of the formulations. In ex vivo drug permeation studies, the formulation containing the BH-Cyc complex has been found to have the highest drug passage among the developed formulations. In the bacterial keratitis model formed in New Zealand albino rabbit eyes in in vivo studies, both TSA-coated inserts and inserts containing the BH-Cyc complex provide improvement in treatment scores as much as the commercial drug (Besivance®) which was applied 3 times a day, even inserts administered one time during treatment period.