Development of Functional Poly(alpha-hydroxy acids) for Drug Delivery Application

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DESCRIPTION (provided by applicant): Poly(1-hydroxy acids) (PHAs) are a class of biodegradable and biocompatible polymers that have been widely used in drug delivery. Well-known examples of PHAs include poly(lactide), poly(glycolide) and poly(lactide-b-glycolide). They are readily available from inexpensive, renewable resources through ring- opening polymerizations of lactide, glycolide and a mixture of lactide and glycolide, respectively. One drawback of these conventional PHAs, however, is their lack of side-chain functionality, which makes it difficult for conjugation of enabling ligands to the PHAs or for fine-tuning of the physical and pharmacological properties of PHA-derived delivery vehicles through side-chain modifications. Syntheses of some extensively used PHAs, such as poly(lactide-b-glycolide), typically involve elevated temperature, which leads to PHAs with poorly controlled molecular weights (MWs) and broad molecular weight distributions (MWDs). In this application, we aim to develop method that will allow facile preparation of PHAs with controlled molecular weight and functionality will lead to useful biomaterials for drug delivery and tissue engineering. We then aim to develop paclitaxel-conjugated PHAs via drug-initiated polymerization for preparing PHA-paclitaxel nanoconjugate drug delivery vehicles. Compared to nanoencapsulates, conventional polymeric nanoparticles that have been widely used in cancer drug delivery, nanoconjugates have much higher drug loading and drug loading efficiency, and show controlled release profiles with significantly reduced drug burst release. By integrating PHA to the formulation of NCs, the PHA-paclitaxel nanoconjugates are expected to have substantially improved tunability of drug release kinetics and have functional groups that are critical for their application in cancer drug delivery. PUBLIC HEALTH RELEVANCE: Poly(1-hydroxy acids) (1-PHAs) are a class of biodegradable and biocompatible polymers that have been widely used in drug delivery. One drawback of the 1-PHAs is their lack of side-chain functional groups. Addressing this issue, we aim to develop methodology that allows facile, controlled synthesis of 1-PHAs bearing essentially any proteolytic side chains for drug delivery applications.