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

Encapsulation of bioactive peptides in slow-release particles is complex and relies on organic solvents. Here, the authors absorb peptides in a polymer phase from water, creating a simple low-cost encapsulation process in a class of polymer depot. Poly(lactic-co-glycolic acid) (PLGA) long-acting release depots are effective for extending the duration of action of peptide drugs. We describe efficient organic-solvent-free remote encapsulation based on the capacity of common uncapped PLGA to bind and absorb into the polymer phase net positively charged peptides from 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 (R). 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 methods. In certain cases, in vitro and in vivo performance of remote-loaded PLGA microspheres exceeded that relative to marketed products. Remote absorption encapsulation further removes the need for a critical organic solvent removal step after encapsulation, allowing for simple and cost-effective sterilization of the drug-free microspheres before encapsulation of the peptide.

Automated summary

Encapsulation of bioactive peptides in slow-release particles is achieved through a simple and low-cost method of remote encapsulation using polymer phase absorption. This technique allows for extended duration of action of peptide drugs and eliminates the need for organic solvents and critical removal steps.