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 &mu / m and ca 95 &mu / m, 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 &mu / m) 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.
| Identifer | oai:union.ndltd.org:METU/oai:etd.lib.metu.edu.tr:http://etd.lib.metu.edu.tr/upload/12612914/index.pdf |
| Date | 01 February 2011 |
| Creators | Ocal, Yigit |
| Contributors | Keskin, Dilek |
| Publisher | METU |
| Source Sets | Middle East Technical Univ. |
| Language | English |
| Detected Language | English |
| Type | M.S. Thesis |
| Format | text/pdf |
| Rights | To liberate the content for public access |
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