Biodegradable nanoparticles based on linoleic acid and poly(beta-malic acid) double grafted chitosan derivatives as carriers of anticancer drugs.
Novel chitosan derivatives carrying linoleic acid (LA) as hydrophobic moieties and poly(beta-malic acid) (PMLA) as hydrophilic moieties (LA/PMLA double grafted chitosan, LMC) were synthesized. It self-assembled into nanoparticles of 190-350 nm in water, which carried negative surface charges in physiological pH. The critical aggregation concentration of the LMC deceased with an increase in the LA content. Paclitaxel (PTX) was loaded into the LMC nanoparticles with a high loading efficiency and the maximum loading capacity of 9.9 +/- 0.4%. PTX-LMC nanoparticles exhibited a sustained release within 24 h in pH 7.4 phosphate-buffered saline (PBS), and the release rate was affected by the LA content and PMLA length. Hemolysis and acute toxicity assessment indicated that the LMC nanoparticles were safe drug carriers for i.v. administration. Additionally, PTX-LMC showed significantly potent tumor inhibition efficacy relative to that of TAXOL in S-180 bearing mice. Therefore, the LMC nanoparticles could be an effective and safe vehicle for systemic administration of hydrophobic drugs, especially PTX.
Zhao
Ziming
Z
State Key Laboratory of Genetic Engineering, Department of Pharmaceutical Sciences, School of Life Sciences, Fudan University, Shanghai, China.
He
Miao
M
Yin
Lichen
L
Bao
Jiamin
J
Shi
Lili
L
Wang
Bingqing
B
Tang
Cui
C
Yin
Chunhua
C
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D048271:Chitosan / Q000031:analogs & derivatives / Q000737:chemistry* / Q000378:metabolism; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems; D005260:Female; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D019787:Linoleic Acid / Q000737:chemistry* / Q000378:metabolism; D046911:Macromolecular Substances / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D008293:Malates / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D008422:Materials Testing; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D010316:Particle Size; D011108:Polymers / Q000737:chemistry* / Q000378:metabolism; D013499:Surface Properties; D014867:Water / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
D000972:Antineoplastic Agents, Phytogenic; D001672:Biocompatible Materials; D004337:Drug Carriers; D046911:Macromolecular Substances; D008293:Malates; D011108:Polymers; C121060:poly(malic acid); D014867:Water; D048271:Chitosan; D019787:Linoleic Acid; D017239:Paclitaxel