(276e) PLGA-Zwitterionic Block Copolymers: Synthesis, Characterization, and Application for Drug Delivery

Stability and functionability are two key issues for nanoparticle (NP) -based pharmaceutical applications. At present, polyethylene glycol (PEG) is widely used as coating materials for this purpose. For example, poly(D,L-lactic-co-glycolic acid) (PLGA) -PEG copolymers are developed to encapsulate hydrophobic drug into NPs with targeting ligands immobilized on the NP surface. Recently, it is found that zwitterionic poly(carboxybetaine) (pCB) has good stealthy properties like PEG. Furthermore, pCB has an abundance of functional groups (each monomer has one COOH group in its side chain) for ligand functionalization while each PEG polymer has only one functional group (e.g., COOH) at its end. These unique features render pCB a promising NP coating platform to solve existing stability and multi-functional problems in pharmaceutical industry.

In this work, PLGA is chosen as base materials to package drug for controlled release purposes. PLGA-b-PCB is synthesized and is used to form NPs (with docetaxel, a model drug) via nanoprecipitation method. A novel synthetic route and modified nanoprecipitation protocols are used to fabricate copolymers and NPs, respectively, due to the huge difference in polarity between hydrophobic PLGA and zwitterionic PCB. The resulted NPs are well controlled in sizes (e.g. 150 nm) and super stable in biological medium. Furthermore, The NPs can efficiently retain the sizes after high-speed centrifugation and even after lyophilization, only with brief re-suspension (no sonication required). This superiority can hardly be achieved by any existing NP systems (e.g. PLGA-PEG NPs) without additives such as 10% sucrose. Drug loading and releasing profiles are also studied to tailor PLGA-PCB NPs for pharmaceutical applications. How zwitterionic nature contributes to the super stability and influences drug delivery behaviors are also discussed.