Preparation and characterization of biodegradable amphiphilic polymers and nanoparticles with high protein loading capacity

Multiblock copolymers containing carboxyl groups in the side-chains and at the chain ends were prepared from ABA triblock copolymers of ε-caprolactone, or lactide (as A block), and ethylene glycol (as B block). ABAn multiblock copolymers were prepared after chain-end functionalization and chain extension with pyromellitic dianhydride. A series of polymers were synthesized by varying the poly(ethylene glycol) and polyester molecular weight and the chirality of the lactide. Nuclear magnetic resonance analysis was used to confirm free carboxyl groups in the polymer backbone and at the chain ends. Thermal analysis indicated that the presence of pyromellitic dianhydride residues interfered not only with the formation of crystalline phases but also with the thermal degradation of chain-extended polymers. The biocompatibility of these amphiphilic polymers as evaluated with mouse embryo fibroblasts was acceptable. Both the parent ABA triblock copolymers and the carboxylated polymers were processed into nanoparticles. Depending on the polymer structure and reaction conditions, a narrow size nanoparticle distribution from ~10 to 250 nm was obtained. The nanoparticles were loaded with 60%–90% albumin and released 80%–90% of the albumin absorbed. Overall, this system was found to be well suited for the preparation of high-capacity injectable protein drug delivery.