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.
Biodegradable poly（L-lactide-r-trimethene carbonate） copolymers （P（LLA-co-TMC）） with different compositions were synthesized. The degradation of the copolymers was carried out in phosphate buffer saline solutions （pH = 7.4） at 37℃. The compositions, structure and properties of the copolymers in degradation were characterized with IH-NMR, DSC, XRD, GPC, and SEM. The weight loss of the P（LLA-co-TMC） 50/50 was much faster than that of P（LLA-co-TMC） 85/15 and PLLA homopolymer. Interestingly, though the molecular weight of the compolymers decreased greatly during degradation, the compositions were rarely varied. After long time degradation, the PLLA segments were induced to crystallize in the P（LLA-co-TMC） 85/15 copolymer. The SEM observation of the surface and cross-section of P（LLA-co- TMC） 85/15 copolymer films found it was similar to the bulk degradation of PLLA homopolymer.
Inorganic polyhedral oligomeric silsesquioxane （POSS） was used as the core for the synthesis of poly（t- lysine） peptide dendrimer via copper-catalyzed azide-alkyne click chemistry. The inorganic/organic composite dendrimer was characterized by MS, 1H NMR, FTIR, GPC and DLS.
The use of nanotechnology in drug-delivery systems(DDS) is attractive for advanced diagnosis and treatment of cancer diseases. Biodegradable polymeric nanoparticles, for example, have promising applications as advanced drug carriers in cancer treatment. In this review, we discuss the development of drug-delivery systems based on an amphiphilic principle mainly conducted by our group for anti-cancer drug delivery. We first briefly address the synthetic chemistry for amphiphilic biodegradable polymers. In the second part, we summarize progress in the application of self-assembled polymer micelles using amphiphilic biodegradable copolymers as anti-tumor drug carriers.
α-Cyclodextrin/poly(ethylene glycol)(α-CD/PEG) polyrotaxane nanoparticles were prepared via a self-assembly method. Anticancer drug methotrexate(MTX) was loaded in the nanoparticles. The interaction between MTX and polyrotaxane was investigated. The formation, morphology, drug release and in vitro anticancer activity of the MTX loaded polyrotaxane nanoparticles were studied. The results show that the MTX could be efficiently absorbed on the nanoparticles, and hydrogen bonds were formed between MTX andα-CDs. The typical channel-type stacking assembly style of polyrotaxane nanoparticles was changed after MTX was loaded. The mean diameter of drug loaded polyrotaxane nanoparticles were around 200 nm and the drug loading content was as high as about 20%. Drug release profiles show that most of the loaded MTX was released within 8 hours and the cumulated release rate was as high as 98%. The blank polyrotaxane nanoparticles were nontoxicity to cells. The in vitro anticancer activity of the MTX loaded polyrotaxane nanoparticles was higher than that of free MTX.
