Polymer micelles for the protection and delivery of specialized pro-resolving mediators
Mitchell de Prinse, Ronghui Qi, Brian G. Amsden
Abstract
Specialized pro-resolving mediators (SPMs) are being considered for the treatment of chronic inflammatory diseases. However, these polyunsaturated fatty acids are prone to oxidation and as a result have a short biological half-life. It was reasoned that a micelle formulation would provide sustained delivery of SPMs while providing protection from oxidation. Thus, micelle formulations were prepared with poly(ethylene glycol) (PEG) as the hydrophilic block and poly(trimethylene carbonate) (PT) containing unsaturated pendant groups, specifically benzyloxy (BT) and sorbate (ST) groups, as the hydrophobic block. The potential of these micelles was assessed using linoleic acid as a model SPM. Loading into a micelle core reduced the extent of oxidation of the model SPM and a sustained release of non-oxidized model drug was achieved for up to 20 days in vitro from the PEG-P(T-BT) micelles. These micelles were also non-cytotoxic over a wide concentration range, demonstrating the potential of this formulation for effective SPM release in vivo.