Synthesis of polymeric nano-objects for drug delivery applications.

The morphology of polymeric nanoparticles has been identified as one of the main factors affecting the drug loading capacities and biological processes in drug delivery applications. Therefore, controlling the morphology of nanoparticles becomes the main key to obtain specific morphology in order to improve the effectiveness of nanoparticles as drug carriers. In the present work, two alternative approaches to prepare polymeric nano-objects of various morphologies have been developed by using microporous membrane technology (Shirasu Porous Glass (SPG) membranes). Poly(oligoethylene glycol acrylate)-b-polystyrene (POEGA-b-PSt) diblock copolymers of different block lengths were prepared by RAFT polymerization. The first approach entails self-assembly of amphiphilic diblock copolymers employing an SPG-based system where the two liquids are miscible, i.e. an emulsion is not generated. Self-assembly using SPG membrane technology was conducted by first dissolving the polymer in tetrahydrofuran, followed by continuous passage of this copolymer solution through the membrane pores into the aqueous phase. In the second approach, polymeric nano-objects were generated through a solvent evaporation technique. The block copolymer is first dissolved in a water-immiscible organic solvent (chloroform), which is then emulsified with aqueous surfactant solution to obtain emulsion droplets. The solvent is subsequently removed by evaporation, resulting in an increase of the amphiphilic block copolymer concentration in the droplets. Results from both approaches indicate that it is possible to conveniently tune the nano-object morphology via the process parameters of pressure and pore size for a given formulation. The techniques developed were then employed to encapsulate hydrophobic drugs within various polymeric nano-objects. This study demonstrates the feasibility of using self-assembly of amphiphilic block copolymers in tandem with microporous membrane technology as a novel approach to