Synthesis and Characterization of Six-Arm Star Poly(delta-valerolactone)-block-Methoxy Poly(ethylene glycol) Copolymers

摘要

Novel amphiphilic six-arm star diblock copolymers based on biocompatible and biodegradable poly-(delta-valerolactone) (PVL) and methoxy poly(ethylene glycol) (MePEG) were synthesized by a two-step process.First,the hydrophobic star-shaped PVL with hydroxyl terminated functional groups was synthesized using a multifunctional alcohol,dipentaerythritol (DPE),as the initiator and fumaric acid as the catalyst.The amphiphilic six-arm star copolymer of poly(delta-valerolactone)-b-methoxy poly(ethylene glycol),(PVL-b-MePEG)_6,was then synthesized by coupling the hydroxyl terminated six-arm PVL homopolymer with a-methoxy-omega-chloroformate-poly(ethylene glycol) (MePEG-COCl).~1H NMR and GPC analyses confirmed the successful synthesis of star-shaped copolymers with predicted compositions and narrow molecular weight distributions.DSC analysis revealed that the glass transition temperatures of the star PVL homopolymers with M_n between 5000 and 49 000 are not dependent on their molecular weights,whereas the melting temperatures of both the PVL homopolymers and the amphiphilic (PVL-b-MePEG)6 copolymers increase with an increase in the PVL molecular weight.Micelles were prepared from the (PVL-WePEG)_6 copolymers via the dialysis method and found to have effective mean diameters ranging from 10 to 45 nm,depending on the copolymer composition.In addition,the (PVL-b-MePEG)_6 copolymers having lower PVL content were found to form micelles with a narrow monomodal size distribution,whereas the copolymers having higher PVL content tended to form aggregates with a bimodal size distribution.The noncytotoxicity of the copolymers was also confirmed in CHO-K1 fibroblast cells using a cell viability assay,indicating that the (PVL-b-MePEG)_6 copolymers are suitable for biomedical applications such as drug delivery.