Novel poly{(lactic acid)-co-[(glycolic acid)-alt-(L-glutamic acid)]}-g-monomethyl poly(ethylene glycol) (PLGGE) micelles were prepared and used as carriers for anti-tumor drug delivery. Three PEGylated PLGG copolymers (PLGGE2000, PLGGE1100 and PLGGE500) were characterized by XRD, TG and DSC. The critical micelle concentrations (CMCs) of the amphiphilic copolymers were 1.04, 0.55 and 0.13 μg/mL, respectively. The TEM, AFM and DLS measurements revealed that the micelles were homogeneous spherical nanoparticles with the diameters ranged from 50 to 150 nm when THF was used as solvent in the preparation of the micelles. Interestingly, extended cylindrical micelles were obtained using CHCl 3 as solvent. The micelles could trap doxorubicin (DOX) in the core with the highest drug loading content up to 23.7%. The mean diameter of drug loaded micelles was much bigger than that of blank micelles. The in vitro drug release of the micelles was diffusion-controlled release within the first 36 h and initial burst release was not obvious. However, after 36 h, the release rate in pH 5.0 was faster than that in pH 7.4 due to the degradation. The PLGGE micelles were nontoxic to both NIH 3T3 fibroblasts and HepG2 cells. The in vitro cytotoxicity against HepG2 cells demonstrated that the drug loaded micelles exhibited high inhibition activity to cancer cells. CLSM observation of HepG2 cells showed that DOX released from the micelles could be delivered into cell cytoplasm and cell nuclei. PLGGE micelles are potential promising carriers for anti-tumor drug delivery.
An anti-tumor drug doxorubicin was encapsulated in micelles of poly（ethylene glycol）-b-poly（2,2-dihydroxyl- methyl propylene carbonate） （PEG-b-PDHPC） diblock copolymers. The morphololgy of both blank miceiles and drug loaded micelles was characterized by TEM. The in vitro drug release profiles of micelles were investigated, The cytotoxicity of the micelles was evaluated by incubating with Hela tumor cells and 3T3 fibroblasts. The drug loaded micelles were co-cultured with HepG2 cells to evaluate the in vitr9 anti-tumor efficacies. The results showed that the mean sizes of both micelles with different copolymer compositions increased after being loaded with drugs. The drug release rate of PEG45-b-PDHPC34 micelles was faster than that of mPEGt14-b-PDHPC26 micelles. Both of the two block copolymers were non-toxic. The confocal laser scanning microscopy a：ad flow cytometry results showed that both the drug loaded micelles could be internalized efficiently in HepG2 cells. The PEG45-b-PDHPC34 micelles exhibited higher anti-tumor activity comparing to mPEGxla-b-PDHPC26 micelles.
This paper reports the synthesis and drug delivery properties of a novel supramolecular nanoparticle.α-Cyclodextrins(α-CD) were threaded on cinnamic acid modified poly(ethylene glycol) to form inclusion complex nanoparticles by supramolecular self-assemble.The anti-tumor drug doxorubicin was loaded in the nanoparticles and released in vitro to study the drug release behavior and the anti-tumor effects.The structure and morphology of the nanoparticles were characterized by nuclear magnetic resonance,X-ray diffraction,ultraviolet absorbance,dynamic laser scattering,scanning electronic microscopy,transmission electron microscopy and atom force microscopy.The distribution of the drug loaded nanoparticles in cells and the anti-tumor effects were studied by confocal laser microscopy.The results demonstrate that the supramolecular nanoparticle is biocompatible and it is a promising carrier for drug delivery systems.
LI Yuan,JI Li,WANG Gang,SONG LiQing,HE Bin,LI Li,NIE Yu,WU Yao & GU ZhongWei National Engineering Research Center for Biomaterials,Sichuan University,Chengdu 610064,China
