Keratokonus Tedavisinde Riboflavin’in Girişimsel Olmayan (“Epi-On”) Teknik ile Korneaya Taşınması İçin Oküler İlaç Taşıyıcı Platformların Tasarlanması ve İn Vitro-İn Vivo Değerlendirilmesi

Abstract

Aytekin E. Design and In vitro - In vivo Evaluation of Ocular Drug Delivery Platforms for the Delivery of Riboflavin by Noninvasive (“Epi-On”) Technique in the Treatment of Keratoconus, Hacettepe University Graduate School of Health Sciences, Pharmaceutical Technology Programme, Ph.D Thesis, Ankara, 2020. Keratoconus is an eye disease that is progressive and can result in corneal transplantation if effective treatment is not provided. The most commonly used method in the clinic for the treatment of the disease is the corneal cross-linking procedure. However, since riboflavin cannot pass through the corneal epithelium, in this procedure, the epithelial layer on the eye is first removed by surgical operation. This causes many complications in the patient. To overcome this problem, hydrogel, nanostructured lipid carrier (NLT) and co-crystal formulations containing riboflavin (RB) or riboflavin-5-phosphate sodium (RT) which do not need the removal of the epithelial layer, were developed and evaluated in vitro, ex vivo and in vivo. In ex vivo drug permeation studies, it was determined that co-crystal formulations containing mannitol and NLT formulations containing positively charged RT provide higher drug transition. In ex vivo corneal drug acumulation studies, NLT formulations containing RB were found to be superior to other groups. In vivo studies, it has been found that formulations containing RB provide higher corneal drug concentrations than formulations containing RT. It was found that the most promising formulation developed in in vivo biomechanical studies was the thermosensitive gel formulation containing RT and Transcutol P (THJ-TP). Although this formulation is applied every 15 minutes, it has been found that it is statistically significantly more effective than MedioCROSS TE, which is applied every two minutes and developed in accordance with the “epi-on” method (without epithelium scraping).