(168l) Delivery of Rapamycin and Basic Fibroblast Growth Factor Via Hybrid-Hydrogel for Vascular Healing

The controlled co-delivery an anti-proliferative drug, rapamycin (RAP), in conjunction with a pro-angiogenic growth factor, FGF-2, from an abluminally placed PEG hydrogel could ameliorate inflammation, while promoting angiogenesis following surgical intervention for vascular disease. Here, injectable PEG-liposome hydrogels have been engineered to deliver RAP, encapsulated in liposomes, and FGF-2, multivalently bound to low molecular weight heparin for sustained release, to study their effect on human aortic adventitial fibroblast (AoAF) proliferation and cytokine expression. PEG-liposome hydrogels were formed via the Michael-type addition between thiol and maleimide functionalized components. The cumulative release of both RAP, loaded into the liposomes during formation, and FGF-2 from the hydrogels was determined via spectrophotometric analysis and ELISA, respectively. The effect of the therapeutics following release was tested in-vitro on adventitial aortic fibroblasts (AoAFs) for seven days. RAP and FGF-2 were successfully delivered from PEG hydrogels and remained bioactive for the course of the experiment. AoAFs exhibited decreased proliferation when treated with released RAP, and increased proliferation and TIMP-1 expression when treated with released FGF-2 indicating that the sustained delivery of these therapeutics from the hydrogel can impact proliferation and angiogenic modulators.