Show/Hide Menu
Hide/Show Apps
anonymousUser
Logout
Türkçe
Türkçe
Search
Search
Login
Login
OpenMETU
OpenMETU
About
About
Açık Bilim Politikası
Açık Bilim Politikası
Frequently Asked Questions
Frequently Asked Questions
Browse
Browse
By Issue Date
By Issue Date
Authors
Authors
Titles
Titles
Subjects
Subjects
Communities & Collections
Communities & Collections
Development and characterization of cortisone derivative drugcarrying polymeric microspheres
Download
index.pdf
Date
2011
Author
Öcal, Yiğit
Metadata
Show full item record
Item Usage Stats
10
views
2
downloads
In this study, it is aimed to develop an injectable controlled release system of PCL and P(L,DL)LA microspheres loaded with TA and/or Ral for local treatment of rheumatoid arthritis which will avoid from systemic side effects of traditional administration and eliminate problems caused by direct local injections. Rheumatoid arthritis (RA) is a chronic, systemic, autoimmune disorder that most commonly causes inflammation and tissue damage in joints and tendon sheaths. Current strategies for the disease are mainly towards relieving symptoms and increasing mobility. The microsphere form drug delivery systems were developed to enhance the treatment success of rheumatic diseases by providing these agents alone or together for long terms without causing systemic or local site effects upon injection to the RA joints. Microspheres were prepared with s/o/w solvent evaporation technique and optimized to achieve a suitable size for joint application, to sustain the delivery of the drug(s), to provide required amount of the agent with feasible amount of microsphere. In order to manage these, microspheres prepared with different combinations of polymers and drugs were examined for particle size analysis, surface and structural characterizations, time related drug release properties, and drug loading capacities. In vitro cytotoxicity tests using 3T3 fibroblast cells were done to evaluate the biocompatibility of drug loaded PCL microspheres. The degradation of polymers were conducted and evaluated by GPC analysis. In PCL:TA microspheres, as polymer:drug ratio decreased (from 10:1 towards 10:4), namely as the drug partition increased, it was seen that encapsulation efficiency and loading percentages increased. Meanwhile, percent release of the drug decreased, indicating more prolonged release. Among all microspheres, PCL:TA 10:4 and PCL:Ral 10:2 were found to be the most appropriate for dual release in terms of release values (ca 21% and 0.09%, respectively), loadings (ca 27% and ca 13%, respectively) and mean particle size values (ca 100 μm and ca 95 μm, respectively). After release studies, microspheres preserved their sphericity. These selected polymer:drug groups also represented no cytotoxic effect. The microspheres for dual drug study (PCL:TA:Ral 10:4:2) released app. 55% of its TA and 0.29% of Ral at the end of 4 weeks. Drug loading capacities of these microspheres were found to be ca 14% for TA and 8% for Ral. Furthermore, with dual loading case, smallest mean particle size (68 μm) could be obtained among all studied groups. P(L,DL)LA microspheres caused high viscosity problems during microsphere preparation steps and resulted in the slowest release, which was unfavorable for the aim of the study. To our knowledge there is no microsphere study reported with P(L,DL)LA in literature. The TA and Ral delivery systems with PCL and P(L,DL)LA were developed and studied for the first time in literature and they were optimized for RA treatment purposes. The potential of these systems, should be further tested in experimental animal models of RA.
Subject Keywords
Polymeric drugs.
URI
http://etd.lib.metu.edu.tr/upload/12612914/index.pdf
https://hdl.handle.net/11511/20361
Collections
Graduate School of Natural and Applied Sciences, Thesis