Synthesis, Characterization and Pharmacokinetics of Irinotecan-loaded Nanoparticles
LATIN AMERICAN JOURNAL OF PHARMACY(2018)
摘要
A novel graft copolymer methoxy poly(ethylene-glycol)-g-poly(acrylic acid)-g-poly( lactide) (mPEG-PAA-PLA) was synthesized as drug carriers. The chemical structure was characterized by FT-IR and H-1 NMR. mPEG-PAA-PLA could easily self-assemble to form nanoparticles in an aqueous environment and exhibited a low critical micellar concentration and a high drug encapsulation efficiency. The size of the nanoparticles measured by DLS demonstrated that the size distribution was narrow and the average diameter was less than 150 nm. The morphology of the nanoparticles observed by AFM indicated that the nanoparticles exhibited a smooth surface and distinct spherical shape. Both in vivo and in vitro drug release experiments showed the nanoparticles had sustained release effects. The main pharmacokinetic parameters of CPT-11 injection and CPT-11/mPEG-g-PAA-g-PLA nanoparticles were as follows: t(1/2) were 0.71 and 1.45 h, AUC(0 ->infinity) were 5.49 and 17.90 mu g.h/mL, MRT were 0.56 and 3.09 h. In conclusion, mPEG-PAA-PLA copolymer could be developed as one of the promising vectors to anti-cancer agents for chemotherapeutics.
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关键词
amphiphilic graft copolymer,irinotecan,long-circulation,passive targeting,self-assembly nanoparticle
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