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Development and characterization of ...

Liang, Sanching Linda.

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Development and characterization of methotrexate loaded poly(L-lactic acid) microspheres for the treatment of rheumatoid arthritis.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Development and characterization of methotrexate loaded poly(L-lactic acid) microspheres for the treatment of rheumatoid arthritis./
Author:	Liang, Sanching Linda.
Description:	268 p.
Notes:	Source: Dissertation Abstracts International, Volume: 67-03, Section: B, page: 1393.
Contained By:	Dissertation Abstracts International67-03B.
Subject:	Health Sciences, Pharmacy. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=NR13016
ISBN:	9780494130162

Development and characterization of methotrexate loaded poly(L-lactic acid) microspheres for the treatment of rheumatoid arthritis.
Liang, Sanching Linda.

Development and characterization of methotrexate loaded poly(L-lactic acid) microspheres for the treatment of rheumatoid arthritis. - 268 p.

Source: Dissertation Abstracts International, Volume: 67-03, Section: B, page: 1393.

Thesis (Ph.D.)--The University of British Columbia (Canada), 2006.

MTX loaded PLLA2k microspheres were shown to be well tolerated in the rabbit knee joints and provide a controlled, localized delivery of MTX into the joint cavity following intra-articular injection.

ISBN: 9780494130162Subjects--Topical Terms:

1017737
Health Sciences, Pharmacy.

Development and characterization of methotrexate loaded poly(L-lactic acid) microspheres for the treatment of rheumatoid arthritis.
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100 1 $a Liang, Sanching Linda. $3 1288335
245 1 0 $a Development and characterization of methotrexate loaded poly(L-lactic acid) microspheres for the treatment of rheumatoid arthritis.
300 $a 268 p.
500 $a Source: Dissertation Abstracts International, Volume: 67-03, Section: B, page: 1393.
502 $a Thesis (Ph.D.)--The University of British Columbia (Canada), 2006.
520 $a MTX loaded PLLA2k microspheres were shown to be well tolerated in the rabbit knee joints and provide a controlled, localized delivery of MTX into the joint cavity following intra-articular injection.
520 $a Methotrexate (MTX) has shown anti-inflammatory effects in the treatment of rheumatoid arthritis. Attempts by other groups have been made to improve the efficacy and reduce toxicity by administering the drug intra-articularly, but the outcomes were not successful due to rapid clearance of the drug from the joint cavity. MTX loaded polymeric microspheres may provide a controlled release drug delivery system to maintain an effective concentration of MTX in the joint cavity. The goals were to develop MTX loaded microspheres and to determine the in vivo biodistribution and efficacy following intra-articular injection in rabbit joints. MTX loaded poly(L-lactic acid) microspheres (size range 33-110 mum) manufactured from poly(L-lactic acid) with an average molecular weight of 2000 g/mole (PLLA2k) showed good tolerability in rabbit joints. The in vitro drug release profiles of MTX loaded PLLA2k microspheres demonstrated a rapid burst phase with more than 50% of drug being released within 5 days followed by a slow release phase.
520 $a Pharmacokinetics of MTX following intra-articular injection of both 1.5 mg and 10 mg doses of either MTX solution or MTX loaded microspheres (33-110 mum) were investigated in healthy rabbits. Plasma concentration peaked at 15 min (tmax) following intra-articular injection, and the maximum plasma concentration (Cmax) for rabbits injected with MTX solution was 5 fold higher than for rabbits injected with MTX microspheres. Approximately 70% of injected MTX dose was excreted in the urine of the rabbits injected with MTX solution while only 12% of the dose was excreted in the urine of the rabbits injected with MTX microspheres 24 h following intra-articular injection.
520 $a In vivo efficacy of intra-articular MTX loaded PLLA2k microspheres (33-110 mum) or MTX solution was evaluated using an antigen-induced arthritis rabbit model. Arthritis was successfully induced in the joints of rabbits with the observation of histopathological features resembling rheumatoid arthritis. Based on the degree of swelling of the knee joints and a system of scoring the pathological features of the disease, there was no significant difference between MTX solution and microspheres treated groups compared to phosphate buffered saline (control) animals. The lack of therapeutic responses to MTX loaded microspheres treatment was likely due to the severity of the disease induced and insufficient length of the observation period.
590 $a School code: 2500.
650 4 $a Health Sciences, Pharmacy. $3 1017737
690 $a 0572
710 2 0 $a The University of British Columbia (Canada). $3 626643
773 0 $t Dissertation Abstracts International $g 67-03B.
790 $a 2500
791 $a Ph.D.
792 $a 2006
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=NR13016