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INFLUENCE OF POLYMER MATRIX STRUCTURE ON CONTROLLED RELEASE OF IDARUBICIN IN A CSF AND SALINE SOLUTION.
|Janusz Kasperczyk 1,2, Katarzyna Stokłosa 1, Piotr Dobrzynski 2, Waldemar Przybyszewski 3, Marek Jurkowski 3, Krystyna Trzepietowska-Stępień 1, Adam Wilczok 1, Maria Sokól 3
1. Śląska Akademia Medyczna, ul. Narcyzów 1, Sosnowiec 41-200, Poland
|In this study, the use of biodegradable copolymers such as poly(glycolide-co-lactide), poly(lactide-co-ε-caprolactone) and poly(glycolide-co-ε-caprolactone) for incorporation of idarubicin to polymer matrices with variable molar ratio of glycolydyl, lactydyl and ε-oxycaproyl units is investigated. The effect of different microstructure of polymer chain, on in vitro idarubicin release from matrices in two types of fluids: artificial cerebrospinal fluid and saline solution and in vivo idarubicin release from matrices in rat implantable with glioma was studied.
Figure 1. Cumulative release of idarubicin from biodegradable copolymers in a CFS observed for 356 days.
Figure 2. Cumulative release of idarubicin from biodegradable copolymer in saline and aCSF solutions observed for about 80 days.
From three types of copolymers the most stable idarubicin release for poly(glycolide-co-ε-caprolactone) with random chains is observed. No burst effect for all biodegradable aliphatic polyesters was confirmed. As expected, type of copolyesters, especially molar ratio of sequences and type of fluids amount of drug release and time of degradation were observed. Microstructure analysis of poly(glycolide-co-ε-caprolactone) matrices with idarubicin determined by 1H NMR. Regular degradation rate by monitoring of such parameters as degree of randomness, average length of sequences and transestrification coefficient of the second mode were confirmed. Presence of idarubicin and metabolites in rat urine and serum weren't observed using NMR in vivo and HPLC measurements. Besides in urine change of glucose, glicine, alanine, histidine, lactate, acetate, citrate, succinate levels weren't also noticed. The result suggest that lack of systemic toxic effects of idarubicin device can be achieved using random poly(glycolide-co-ε-caprolactone) matrix with anthracycline. In this case side effects of chemiotherapy with idarubicin such as inflammation of gastrointestinal mucosa, nausea, chills and cardiotoxicity might be eliminated. In future bioresorbable copolyester devices with idarubicin could be effective and nontoxic therapy of brain gliomas used.
This study was supported by a grant (No. 3/FB/2004) from Foundation of Pharmacetical Sciences Development.
Presentation: Poster at V Multidyscyplinarna Konferencja Nauki o Leku, by Katarzyna Stokłosa
See On-line Journal of V Multidyscyplinarna Konferencja Nauki o Leku
Submitted: 2006-01-30 13:48 Revised: 2009-06-07 00:44