Microgels produced using microfiuidic on-chip polymer blending for controlled released of VEGF encoding lentivectors

摘要

Alginate hydrogels are widely used as delivery vehicles due to their ability to encapsulate and release a wide range of cargos in a gentle and biocompatible manner. The release of encapsulated therapeutic cargos can be promoted or stunted by adjusting the hydrogel physiochemical properties. However, the release from such systems is often skewed towards burst-release or lengthy retention. To address this, we hypothesized that the overall magnitude of burst release could be adjusted by combining microgels with distinct properties and release behavior. Microgel suspensions were generated using a process we have termed on-chip polymer blending to yield composite suspensions of a range of microgel formulations. In this manner, we studied how alginate percentage and degradation relate to the release of lentivectors. Whereas changes in alginate percentage had a minimal impact on lentivector release, microgel degradation led to a 3-fold increase, and near complete release, over 10 days. Furthermore, by controlling the amount of degradable alginate present within microgels the relative rate of release can be adjusted. A degradable formulation of microgels was used to deliver VEGF-encoding lentivectors in the chick chorioallantoic membrane assay and yielded a proangiogenic response in comparison to the same lentivectors delivered in suspension. The utility of blended microgel suspensions may provide an especially appealing platform for the delivery of lentivectors or similarly sized therapeutics.