Nanomicelle with long-term circulation and enhanced stability of camptothecin based on mPEGylated alpha,beta-poly (L-aspartic acid)-camptothecin conjugate.
To enhance the stability and long-term circulation of camptothecin (CPT), mPEGylated alpha,beta-poly (L-aspartic acid)-CPT conjugates were synthesized, and used to fabricate nanomicelle. Firstly, alpha,beta-poly (L-aspartic acid) derivative (PAA-der) containing alkyne groups was synthesized via the ring-opening of PSI with propargyl amine. And then, azide-functionalized CPT derivatives (CPT-N(3)) and azide-terminated poly (ethylene glycol) methyl ether (mPEG-N(3)) were conjugated with PAA-der by click cycloaddition to give mPEG-graft-PAA-CPT conjugates. The formation of mPEG-graft-PAA-CPT nanomicelles was confirmed by fluorescence spectrophotoscopy and particle size measurements. It was found that all the nanomicelles showed spherical shapes with size about 178 nm. MPEG-graft-PAA-CPT nanomicelles showed good storage stability, even incubation at 37 degrees C for 60 days, and improved the stability of CPT lactone form in aqueous media. A steady release rate of CPT was kept for 72h, suggested the great potential of mPEG-graft-PAA-CPT nanomicelles as polymer prodrug of CPT.
Zhang
Weilu
W
Institutes for Advanced Interdisciplinary Research, East China Normal University, 3663# North Zhongshan Road, Shanghai 200062, PR China.
Huang
Jin
J
Fan
Naiqian
N
Yu
Jiahui
J
Liu
Yongbiao
Y
Liu
Shiyuan
S
Wang
Daxin
D
Li
Yaping
Y
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000493:pharmacokinetics; D001224:Aspartic Acid / Q000737:chemistry*; D002166:Camptothecin / Q000737:chemistry* / Q000493:pharmacokinetics; D004339:Drug Compounding; D004355:Drug Stability; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D008956:Models, Chemical; D015394:Molecular Structure; D049329:Nanostructures; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013997:Time Factors
D000972:Antineoplastic Agents, Phytogenic; D008823:Micelles; D011108:Polymers; D001224:Aspartic Acid; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol; D002166:Camptothecin