title: Development of a novel biocompatible poly(ethylene glycol)-block-poly(γ-cholesterol-L-glutamate) as hydrophobic drug carrier.
abstract: A novel biomaterial poly(ethylene glycol)-block-poly(γ-cholesterol-l-glutamate) (mPEG-PCHLG) was designed and synthesized by introducing cholesterol side chains into this pegylated poly(amino acid) copolymers to enlarge the core space to increase the drug capacity. Paclitaxel (PTX) loaded mPEG-PCHLG nanoparticles (PTX-mPEG-PCHLG-Nps) were developed for the first time. The preparation method of nanoparticles was screened and optimized systemically. The optimal PTX-mPEG-PCHLG-Nps with the average diameter of 213.71 nm were constructed through the O/W single-emulsion solvent evaporation method. The entrapment efficiency and drug loading was 38.02 ± 4.51% and 93.90 ± 4.56%, respectively. PTX-mPEG-PCHLG-Nps were spherical and well-dispersed and displayed a dramatic sustained-release property. The in vitro cytotoxicity experiments demonstrated that the blank mPEG-PCHLG nanoparticles had no cytotoxicities on four tumor cell lines including A549, HepG-2, MCF-7 and C26, which implied that mPEG-PCHLG might be biocompatible. PTX-mPEG-PCHLG-Nps obtained the same cell growth inhibition activities as free PTX when incubated with the above tumor cells for 48h. It can be inferred that PTX-mPEG-PCHLG-Nps could probably have higher anticancer efficacy due to the inadequate release of PTX from nanoparticles. PTX-mPEG-PCHLG-Nps achieved the highest antitumor activity in A549 rather than HepG-2, MCF-7 and C26, thus PTX-mPEG-PCHLG-Nps could have a potential application in lung cancer therapy. All the data indicated that mPEG-PCHLG was one of biocompatible biomaterials and worth being widely investigated as hydrophobic antitumor drug carrier.
authors: State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors: Qing
authors: Q
authors: Ma
authors: Bo
authors: B
authors: Li
authors: Yiyi
authors: Y
authors: Yu
authors: Ying
authors: Y
authors: Zhang
authors: Yang
authors: Y
authors: Wu
authors: Wen
authors: W
authors: Ren
authors: Yu
authors: Y
authors: Zheng
authors: Jun
authors: J
authors: He
authors: Yongmei
authors: Y
authors: Xie
authors: Xiangrong
authors: X
authors: Song
authors: Gu
authors: G
authors: He
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002788:Cholesterol Esters / Q000008:administration & dosage / Q000737:chemistry*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry; D010316:Particle Size; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry*; D011099:Polyglutamic Acid / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002788:Cholesterol Esters; D004337:Drug Carriers; C583082:poly(ethylene glycol)-block-poly(gamma-cholesterol-glutamate); D011099:Polyglutamic Acid; D011092:Polyethylene Glycols; D017239:Paclitaxel