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- 저자 : ( Himabindu Ruttala ) (검색결과 1 건)
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( Thiruganesh Ramasamy ),( Bijay Kumar Poudel ),( Himabindu Ruttala ),( Ju Yeon Choi ),( Truong Duy Hieu ),( Kandasamy Umadevi ),( Yu Seok Youn ),( Han Gon Choi ),( Chul Soon Yong ),( Jong Oh Kim ) 영남대학교 약품개발연구소 2016 영남대학교 약품개발연구소 연구업적집 Vol.26 No.-
Nanofabrication of polymeric micelles through self-assembly of an ionic block copolymer and oppositely charged small molecules has recently emerged as a promising method of formulating delivery systems. The present study therefore aimed to investigate the interaction of cationic drugs doxorubicin (DOX) and mitoxantrone (MTX) with the anionic block polymer poly(ethylene oxide)-block-poly(acrylic acid) (PEO-b-PAA) and to study the influence of these interactions on the pharmacokinetic stability and anti-tumor potential of the formulated micelles in clinically relevant animal models. To this end, individual DOX and MTX-loaded polyelectrolyte complex micelles (PCM) were prepared, and their physicochemical properties and pH-responsive release profiles were studied, MTX-PCM and DOX-PCM exhibited a differ-ent release profile under all pH conditions tested. MTX-PCM exhibited a monophasic release profile with no initial burst, while DOX-PCM exhibited a biphasic release, DOX-PCM showed a higher cellular uptake than that shown by MTX-PCM in A-549 cancer cells. Furthermore, DOX-PCM induced higher apoptosis of cancer cells than that induced by MTX-PCM, Importantly, both MTX-PCM and DOX-PCM showed pro-longed blood circulation. MTX-PCM improved the AUC<sub>all</sub> of MTX 4-fold compared to a 3-fold increase by DOX-PCM for DOX, While a definite difference in blood circulation was observed between MTX-PCM and DOX-PCM in the pharmacokinetic study, both MTX-PCM and DOX-PCM suppressed tumor growth to the same level as the respective free drugs, indicating the potential of PEGylated polymeric micelles as effective delivery systems. Taken together, our results show that the nature of interactions of cationic drugs with the polyionic copolymer can have a tremendous influence on the biological performance of a delivery system.
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