Polymers as a Platform for Drug Delivery: Reviewing our Current Portfolio on Poly(lactide-co-glycolide) (PLGA) Microspheres

Abstract

The chemical conjugation or the physical embodiment of therapeutic agents in polymers offers great potential to improve the efficacy and safety of therapies and create novel therapeutic opportunities. This has led to numerous concepts regarding the formulation, the delivery and the targeting of therapeutics. Our current research portfolio in this field includes several projects. In all of them poly(lactide-co-glycolide), PLGA, varying in molecular weight and end-group modification, is used as a delivery platform. In this review we will firstly outline our concept of single-injection vaccines. Instead of the application of repeated booster doses, such vaccines are designed to deliver the antigen in a pulsed or sustained fashion, in such a way that protective humoral and cellular immunity can be achieved after a single injection. In the second polymer-based project we aim at the administration of insulin-like growth factor I (IGF-I), which bears great potential in tissue engineering, e.g. to enhance bone healing. Here we summarize on a PLGA microsphere system for the localized and controlled delivery of IGF-I in order to close bone defects after fracture, pathology or surgery. In a third project we use this polymeric platform for the design of antigen-encoding DNA vaccines designed to preferentially target the most potent antigen presenting cells, i.e. the dendritic cells. Two prime objectives are currently being studied, i) enhancement of phagocytosis of DNA-loaded PLGA microspheres by human-derived dendritic cells, and ii) release of intact plasmid DNA and concomitant transfection of dendritic cells once the PLGA microspheres were successfully phagocytosed.