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

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Polymer Chemistry

Background:

• Poly(lactic-co-glycolic acid) (PLGA) microspheres are established for long-acting peptide drug delivery.
• Traditional encapsulation methods often require organic solvents, complicating manufacturing and sterilization.

Purpose of the Study:

• To develop an efficient, organic-solvent-free remote encapsulation technique for cationic peptides using PLGA.
• To evaluate the in vitro and in vivo performance of peptides encapsulated via this novel method.

Main Methods:

• Utilized uncapped PLGA's capacity to absorb net positively charged peptides from aqueous solution.
• Encapsulated leuprolide and octreotide in low-molecular-weight PLGA 75/25 microspheres without organic solvents.
• Assessed in vitro peptide release over 56 days and in vivo testosterone suppression in rats.

Main Results:

• Achieved slow, continuous release of leuprolide for over 56 days in vitro.
• Demonstrated testosterone suppression in rats comparable to marketed Lupron Depot®.
• Showcased generalizability to other cationic peptides like octreotide with competitive efficiencies.
• Observed superior in vitro and in vivo performance in some cases compared to marketed products.

Conclusions:

• The developed remote absorption encapsulation is an efficient, solvent-free alternative for peptide-loaded PLGA microspheres.
• This method simplifies manufacturing, reduces costs, and allows for pre-encapsulation sterilization of microspheres.
• The technique holds promise for improved long-acting injectable peptide formulations.