(227g) Functional Poly(α-hydroxyl acid)-Based Biomaterials for Drug and Gene Delivery

Biomedical applications of conventional Poly(α-hydroxyl acid)s (PAHAs) have been considerably restricted by their lack of functional groups.  Therefore, recently our group has prepared a variety of PAHAs with pendent functionalities and further converted them into novel polymeric scaffolds for therapeutic delivery.  Several types of well-defined polymer-drug conjugates (PDCs) with PAHA-based backbones and high drug loadings have been prepared.  Among them, the PDCs with drug as monovalent pendent moieties can exhibit sustained drug release behavior, as well as enhanced therapeutic efficacy.  Tertiary amine-functionalized cationic PAHAs have also been synthesized.  With remarkable degradability, low cytotoxicity and the ability to adsorb genes via electrostatic interactions, these cationic PAHAs can serve as novel synthetic vectors to enable highly efficient delivery of plasmid DNA and siRNA. Well-defined PAHA-based nanoparticles and nanocapsules have been obtained by UV-induced thiol-ene cross-linking of allyl-functionalized PAHA-based precursor polymers in transparent miniemulsions.  Specifically, converted from allyl/amine-functionalized PAHAs, cationic PAHA nanocapsules can not only encapsulate drug in their inner cavities but also adsorb genes on their cationic shells.  These nanocapsules can effectively evade multi-drug resistance and co-deliver drug and gene into cancer cells.