(600f) Liposome-Containing Polyethylene Glycol Microgels for Multi-Therapeutic Delivery

Bypass grafting, the primary surgical intervention for coronary artery disease (CAD), results in high failure rates due to intimal hyperplasia, fibrosis, and restenosis. Surgical manipulation of the vessel results in increased proliferation and production of inflammatory cytokines, via adventitial cell activation, which ultimately contribute to these maladaptive responses. Temporally resolved delivery of multiple therapeutics from injectable PEG microgels that target adventitial cell populations throughout the early stages of remodeling post-surgery could regulate vascular healing. We investigate the delivery of small molecules, growth factors, and proteins from PEG microgels. Here, injectable hybrid PEG-liposome microgels (~75µm) have been engineered to deliver cargo encapsulated in liposomes, physically entrapped in the polymer network, and multivalently bound to low molecular weight heparin for sustained release. PEG-liposome microgel synthesis was conducted using a flow-focusing microfluidic device via the Micheal-type addition between four-arm thiol-functionalized PEG (Æ’=4, M_n 5,000 g/mol) four-arm vinyl sulfone functionalized PEG (Æ’=4, M_n 5,000 g/mol), maleimide-functionalized low molecular weight heparin (LMWH-mal), and 10mM maleimide-functionalized liposomes. The presence of the liposomes following microgel synthesis was confirmed via fluorescent labeling. Mechanical characterization of the microgels was performed via atomic force microscopy (AFM) to determine the Young’s modulus. Spectrophotometric analysis, ELISA, and BCA assays were used to generate cumulative release profiles for target/model cargo released over seven days.