Preparation And Properties Of Tamoxifen-Loaded Micelles Of Poly(Ethylene Glycol)-Poly(γ-Benzyl-L-Glutamate)₂ Copolymer

Poly(ethylene glycol)-poly(amino acid) is a kind of amphiphilic copolymer with good biocompatibility and biodegradability, and it has attracted great attention for its application as carrier material for anticancer drug and gene delivery. In this thesis, AB2 type star copolymers of poly(ethylene glycol)-poly(γ-benzyl-L-glutamate)2 (MPEG-(PBLG)2) were synthesized. Blank micelles and TAM loaded micelles were prepared by the dialysis method. Morphologies and properties of the polymeric micelles were investigated. The influence of structure and molecular composition of copolymer on morphologies and properties of the polymeric micelles were discussed. The thesis is composed of three parts as follow:(1) Synthesis and characterization of AB2 type star MPEG-(PBLG)2 copolymerα-methoxy-poly(ethylene glycol) with two primary amino groups atω-terminal was used as an initiator of the ring-opening polymerization of (BLG-NCA). AB2 type MPEG-(PBLG)2 copolymers with various molecular compositions were synthesized. Structure and molecular compositions of MPEG-(PBLG)2 copolymers were confirmed by IR spectra and 1H NMR spectra.(2) Preparation and characterization of MPEG-(PBLG)2 polymeric micellesBlank and tamoxifen (TAM) loaded micelles of MPEG-(PBLG)2 copolymer were prepared by dialysis method. The average size and size distribution of micelles were measured by dynamic light scattering (DLS). The results indicated that the micelle sizes were mostly below 50 nm and influenced by structure and molecular compositions of copolymer. The size of micelles increased after TAM loading. Spherical core/shell structures of the micelles were confirmed by transmission electron microscopy (TEM) and 1H NMR spectra. The critical micelle concentrations (CMC) of copolymer were estimated by fluorescence spectroscopy. The values of CMC were dependent on the structure and molecular compositions of copolymer.(3) Investigation of properties of TAM-loaded MPEG-(PBLG)2 micellesThe drug loading content, entrapment efficiency and in vitro release behavior of TAM-loaded micelles were quantified by high performance liquid chromatography (HPLC). TAM loading content and entrapment efficiency increased with increasing PBLG block length. On the in vitro release study of TAM-loaded micelles, a slow and sustained release behavior was observed. The release rate was influenced by structure and molecular compositions of copolymer as well as pH value of release medium and TAM loading content. In vitro cytotoxicity was evaluated by MTT assay. The result demonstrated that TAM loaded MPEG-(PBLG)2 micelles were a litter more cytotoxic in comparison with free TAM and TAM loaded MPEG-PBLG micelles.