Amphiphilic block copolymers bearing six-membered ortho ester ring in side chains as potential drug carriers: synthesis, characterization, and in vivo toxicity evaluation.
A new type of amphiphilic block copolymers, poly(ethylene glycol)-block-poly(2-methyl-acrylicacid 2-methoxy-5-methyl-[1,3]dioxin-5-ylmethyl ester) (PEG-b-PMME), bearing acid-labile six-membered ortho ester rings in side chains was synthesized by reversible addition-fragmentation chain-transfer polymerization, and the influence of chain length of the hydrophobic PMME block on micelle properties was investigated. The PEG-b-PMME micelles were stable in aqueous buffer at physiological pH with a low critical micelle concentration. Nile Red as a model drug was encapsulated into the micelles to explore the release profiles. The Nile Red-loaded polymeric micelles showed rapid release of Nile Red in weakly acidic environments (pH 5) but slow release under physiological condition (pH 7.4), due to different hydrolysis rate of ortho ester side chains of PEG-b-PMME. The Paclitaxel (PTX)-loaded micelles retained potency in killing lung cancer cells (A549), compared with the free PTX. No obvious toxicity was found in vitro and in vivo after intraperitoneal injection of the micelles, which confirms that the PEG-b-PMME micelles with unique acid-labile characteristic have great potential as nano-scaled carriers for drug delivery.
a College of Pharmacy, Jiangnan University , 1800 Lihu Road, Wuxi 214122 , Jiangsu Province , P.R. China.
Shi
S
Luo
Yangyang
Y
Tao
Rupei
R
Tang
Rui
R
Wang
Weihang
W
Ji
Chun
C
Wang
Youliang
Y
Zhao
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D004952:Esters; D005260:Female; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D008823:Micelles; D041681:NIH 3T3 Cells; D010078:Oxazines / Q000737:chemistry; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D058105:Polymerization; D018675:Toxicity Tests
D004337:Drug Carriers; D004952:Esters; D008823:Micelles; D010078:Oxazines; D010714:Phosphatidylethanolamines; C032000:phosphatidyl-N-monomethylaminoethanol; D011092:Polyethylene Glycols; C044808:nile red; D017239:Paclitaxel
acid-labile; drug carriers; micelles; ortho ester