Synthesis And Micellization Of Biodegradable Polyphosphate Block Copolymer

Amphiphilic copolymers, which could self-assemble into aggregates such as micelles and vesicles, are capable for applications in drug delivery. Polyphosphoesters. exhibiting both distinguished biocompatibility and structural versatility, are potential for biomedical applications. A series of biodegradable amphiphilic copolymers of polyphosphoester were synthesized by ring-opening polymerization of ethyl ethylene phosphate (EEP).The structures of the block copolymers were confirmed by FT-IR,1H-NMR and GPC analysis. Fluorescence measurements were applied to determine the critical micelle concentration (CMC) of the copolymer micelle solutions. The diameter and the distribution of micelles were characterized by dynamic light scattering (DLS) and the shape was perceived using transmission electron microscopy (TEM).First, a series of amphiphilic biodegradable methoxypolyethylene glycol/poly(D,L-lactide)/poly(ethyl ethylene phosphate) (MPEG-b-PLA-b-PEEP) block copolymers were synthesized via ring opening polymerization of ethyl ethylene phosphate using hydroxyl terminated methoxypolyethylene glycol/poly(D,L-lactide) and stannous octoate co-initiation system. FT-IR,1H NMR and GPC were used to demonstrate the structure and their compositions which would be adjusted by alternation of the feeding ratio of initiator and monomer. The self-assembly behavior of these copolymers in aqueous solution was studied by 1H NMR and fluorescence technique, which indicated these copolymers formed micellar structure in aqueous solution with a hydrophobic core of poly(D,L-lactide) and a hydrophilic shell composed of methoxypolyethylene glycol and poly(ethyl ethylene phosphate). The critical micelle concentration (CMC) was in a range of 1.0x10-3mg/mL to 3.2x10-3mg/mL; the size of the micelles was in a range of 97 to 116nm, the size of the micelles reduced with increasing of the proportion of PEEP segments.; TEM images demonstrate that all micelles are spherical.Second, a series of amphiphilic biodegradable 4-arm star-shaped poly(D,L-lactide)/poly(ethyl ethylene phosphate) (ssPLA-b-PEEP) block copolymer were synthesized by ring-opening polymerization of ethyl ethylene phosphate (EEP) with 4-arms star-shaped poly(D,L-lactide) (ssPLA) containing terminal hydroxyl as a macroinitiator using stannous octoate as catalyst. FT-IR,1H NMR and GPC were used to demonstrate the structure and their compositions which would be adjusted by alternation of the feeding ratio of initiator and monomer. The self-assembly behavior of these star-shaped copolymers in aqueous solution was studied by fluorescence technique, which indicated these copolymers formed micellar structure in aqueous solution with a hydrophobic core of star-shaped poly(D,L-lactide) and a hydrophilic shell of poly(ethyl ethylene phosphate). The critical micelle concentration (CMC) was in a range of 1.78x10-4mg/mLto 3.16x10-4mg/mL; the size of the micelles was in a range of 77.7 to 135.1nm, the size of the micelles increased with increasing of the proportion of PEEP segments; TEM images demonstrate that all micelles are spherical.