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Identifier 000421737
Title Προκλινική τεκμηρίωση καινοτόμου συστήματος πλατφόρμας για ενδοϋαλοειδική χορήγηση φλουρμπιπροφαίνης
Alternative Title Pre-clinical documentation of a novel platform system for intravitreal administration of flurbiprofein
Author Μπλαζάκη, Στυλιανή
Thesis advisor Τσιλιμπάρης, Μιλτιάδης
Reviewer Αντιμησιάρη, Σοφία
Τζατζαράκης, Εμμανουήλ
Τσατσάκης, Αριστείδης
Κυμιωνής, Γεώργιος
Θερμού, Κυριακή
Τσατσάνης, Χρήστος
Abstract Intravitreal drug delivery is of great interest for improving the treatment of inflammatory diseases of the posterior part of the eye or of various neurodegenerative diseases. It achieves high levels of drugs in vitreous, while avoiding side effects associated with systemic administration. However, many drugs are rapidly removed from the ophthalmic fluids and frequent readministration is required to ensure satisfactory treatment, increasing the risk of endophthalmitis, cataract formation or retinal detachment. Additionally, certain drugs when administered at available therapeutic concentrations, cause local toxicity, side effects and the possibility of retinal damage. For the above reasons, it is imperative to develop new drug delivery systems, among which liposomes have been shown to improve treatment, significantly reducing toxicity and increasing the time of drug storage in the eye. Compared to other nanosystems (such as polymeric nanodimids), liposomes have a better toxicity/ biocompatibility profile and drug loading capacity but shorter retention times. To address the problem, specific drug retention technology has been developed in liposome-specific formulations, and the ability to extend the residence time of even small molecules has been demonstrated in vitro. Additionally, in preliminary in vivo studies it has been shown that the proposed systems are possibly acceptable and biocompatible with ocular tissues. In this project, the anti-inflammatory drug Flurbiprofen (FB) was used as a model of micromolar drug but also as a drug of interest for the eye. The experimental animals used were pigmented rabbit. The bioavailability, efficacy and safety of the flurbiprofen solution (FB) was initially studied. Then the following slow release systems, which were developed and studied in vitro at the University of Patras in the Laboratory of Pharmaceutical Technology, were studied preclinically; liposomes, hydrogel, liposomal hydrogel, and liposomal platform incorporating the drug of interest (FB). The liposomal hydrogel system FB as well as the liposomal FB platform had the best performance on the bioavailability of FB in the eye. Bioavailability of the drug increased 2.2 and 1.9 times for the liposomal platform system and liposomal hydrogel respectively. Measurable amounts of FB were observed up to 72 hours after intravitreal injection. In the inflammation model, the liposomal 161 platform effectively reduced the inflammation to similar levels to dexamethasone. Concerning the toxicity study no particular findings were found during electrophysiological testing. However, for the liposomal platform, toxicity findings were found depending on the dose of the system studied on histological analysis.
Language Greek
Subject Μη- στεροειδή αντιφλεγμονώδη
Issue date 2019-03-27
Collection   Faculty/Department--School of Medicine--Department of Medicine--Doctoral theses
  Type of Work--Doctoral theses
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