Efficient aqueous remote loading of peptides in poly(lactic-co-glycolic acid)

Abstract Poly(lactic-co-glycolic acid) (PLGA) long-acting release (LAR) depots are effective for extending the duration of action of peptide drugs. New market approvals have been slow with dated organic-solvent-based microencapsulation approaches. We describe efficient organic-solvent-free remote encapsulation based on the capacity of common acid-capped PLGA to bind, and absorb into the polymer phase, net positively charged peptides in aqueous solution after short exposure at modest temperature. Leuprolide encapsulated by this approach in low-molecular-weight PLGA 75/25 microspheres slowly and continuously released peptide for over 56 days in vitro and suppressed testosterone production in rats in an equivalent manner as the 1-month Lupron Depot®. The technique is generalizable to encapsulate a number of net cationic peptides of various size, including octreotide, with competitive loading and encapsulation efficiencies to traditional techniques. In certain cases, in vitro and in vivo performance of remote-loaded PLGA microspheres exceeded that relative to marketed products and displayed important features not currently possible with existing encapsulation strategies.