Prikladnost in vitro modela rožnice za ispitivanje paracelularnog prijenosa oftalmičkog lijeka

master's thesis

• Title (english): The suitability of in vitro corneal epithelial model for studying paracellular transport of ophthalmic drug
• Author: Dejan Kraljić
• Mentor: Jasmina Lovrić (mentor)
• Committee member: Jasmina Lovrić
• Committee member: Anita Hafner
• Committee member: Dubravka Vitali Čepo
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmaceutical technology); Zagreb
• Defense date and country: 2015-09-30, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Ovaj diplomski rad dio je projekta čiji je glavni cilj razvoj i implementacija ekonomičnog in vitro modela epitela rožnice velikog kapaciteta, s obzirom na broj ispitanih uzoraka u jedinici vremena, i zadovoljavajućeg predviđanja bioraspoloživosti lijeka u oku ljudi. Cilj ovog diplomskog rada bio je ispitati prikladnost in vitro modela epitela rožnice za ispitivanje paracelularnog prijenosa. U tu svrhu bilo je potrebno ispitati učinak pospješivača apsorpcije, koji ostvaruju svoj učinak otvarajući čvrste veze, na permeabilnost obilježivača velike molekulske mase. Kao pospješivač apsorpcije korišten je kitozan, kationski polimer koji reverzibilno otvara čvrste međustanične veze. Kao obilježivač paracelularnog prijenosa korišten je dekstran FD-4, fluorescentni obilježivač velike molekulske mase. Ponašanje in vitro modela epitela rožnice uspoređeno je s ponašanjem in vitro modela crijevnog epitela. Mjerenjem transepitelnog električnog otpora potvrđen je učinak kitozana na otvaranje čvrstih veza in vitro epitelnog modela rožnice. Učinka kitozana na otvaranje čvrstih veza bio je ovisan o koncentraciji kitozana. Primjenom kitozana došlo je do povećanja prividnog koeficijenta permeabilnosti (Papp) dekstrana FD-4. Citotoksični učinak kitozana na stanice in vitro modela epitela rožnice isključen je praćenjem metaboličke aktivnosti.

Abstract (english)

This diploma thesis is a part of research project which main goal is the development and implementation of high throughput in vitro corneal epithelial model characterized by good predictability of eye-related bioavailability. The aim of this diploma thesis was to investigate the applicability of in vitro corneal epithelial model for studying the paracellular transport. For that purpose, it was necessary to investigate the effect of absorption enhancers which mechanism of action is based on the opening of tight junctions on the permeability of paracellular markers. Chitosan was chosen as the absorption enhancer due to its known effect of reversible opening of tight junctions. Dextran FD-4 was chosen as the fluorescent macromolecular marker of paracellular transport. The behaviour of in vitro corneal epithelial model was compared with the behaviour of in vitro model of intestinal epithelium. The effect of chitosan was monitored by measuring transepithelial electrical resistance. The effect of chitosan was concentration dependent. Chitosan induced the enhancement of the apparent permeability coefficient of dextran FD-4. Cytotoxic effect of chitosan was excluded by monitoring the cell metabolic activity.

• Keywords: caco-2; citotoksičnost; FD-4; HCE-T; kitozan; permeabilnost
• Keywords (english): caco-2; chitosan; cytotoxicity; FD-4; HCE-T; permeability
• Language: croatian
• URN:NBN: urn:nbn:hr:163:758402
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Access restricted to students and staff of home institution
• Created on: 2016-02-22 11:38:42