title: Construction of nanoparticles based on amphiphilic copolymers of poly(γ-glutamic acid co-L-lactide)-1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine as a potential drug delivery carrier.
abstract: A novel amphiphilic copolymer (γ-PGA-co-PLA-DPPE) containing poly(γ-glutamic acid) (γ-PGA), polylactide (PLA), and 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) segments has been successfully synthesized. The chemical structures of the copolymers were characterized by Fourier-transform infrared spectroscopy (FT-IR), NMR ((1)H NMR, (13)C NMR, (31)P NMR), and thermogravimetric analysis (TGA). In order to estimate the feasibility as novel drug carriers, an anti-tumor model drug, doxorubicin hydrochloride salt (DOX) was encapsulated into the copolymers nanoparticles (NPs) by double emulsion and nanoprecipitation methods. The influence of processing factors on encapsulation efficiency and particle size using double emulsion and nanoprecipitation technique were studied. In addition, the DOX-loaded NPs exhibited pH-dependent drug release profiles in vitro. The cumulative release of DOX-loaded NPs was much faster at pH 5.0 than that at pH 7.4. In vitro cytotoxicity test of DOX-loaded NPs against Hela and C666-1 cells demonstrated that DOX-loaded NPs exhibited effectively time-delayed cytotoxicity. Confocal laser scanning microscopy (CLSM) showed that DOX-loaded NPs accumulated mostly in lysosomes instead of cell nucleus, in contrast to free DOX. Therefore, the copolymer nanoparticles were proved to be an available carrier for anti-tumor drug delivery.
authors.affiliation: National Center for Nanoscience and Technology, Laboratory of Nanobiomedicine and Nanosafety, Division of Nanomedicine and Nanobiology, No. 11 Beiyitiao, Zhongguancun, Beijing 100190, China; School of Basic Medical Sciences of Jiamusi University, Jiamusi 154000, China; The First Affiliated Hospital of Jiamusi University, Jiamusi 154002, China.
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Liu
authors.forename: Shishuai
authors.initials: S
authors.lastname: Su
authors.forename: Fengxiang
authors.initials: F
authors.lastname: Wei
authors.forename: Xianghui
authors.initials: X
authors.lastname: Rong
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Yang
authors.forename: Junxing
authors.initials: J
authors.lastname: Liu
authors.forename: Mingjun
authors.initials: M
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
mesh_terms: D002460:Cell Line; D004317:Doxorubicin / Q000008:administration & dosage; D004337:Drug Carriers; D006801:Humans; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D010714:Phosphatidylethanolamines / Q000008:administration & dosage / Q000737:chemistry*; D011099:Polyglutamic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D013818:Thermogravimetry
chemical_list: D004337:Drug Carriers; D010714:Phosphatidylethanolamines; C511775:poly(gamma-glutamic acid); D011099:Polyglutamic Acid; C007510:1,2-dipalmitoyl-3-phosphatidylethanolamine; D004317:Doxorubicin
keywords: 1,2-Dipalmitoyl-sn-glycero-3-phosphoethanolamine; Anti-tumor activity; Controlled drug release; Delivery system; Doxorubicin; Nanoparticles; Poly γ-glutamic acid