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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
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Μπλαζάκη, Στυλιανή
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Thesis advisor
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Τσιλιμπάρης, Μιλτιάδης
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Reviewer
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Αντιμησιάρη, Σοφία
Τζατζαράκης, Εμμανουήλ
Τσατσάκης, Αριστείδης
Κυμιωνής, Γεώργιος
Θερμού, Κυριακή
Τσατσάνης, Χρήστος
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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.
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Language |
Greek |
Subject |
Μη- στεροειδή αντιφλεγμονώδη |
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Φάρμακα |
Issue date |
2019-03-27 |
Collection
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School/Department--School of Medicine--Department of Medicine--Doctoral theses
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Type of Work--Doctoral theses
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Permanent Link |
https://elocus.lib.uoc.gr//dlib/5/5/7/metadata-dlib-1554190410-627397-15980.tkl
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Views |
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