Coaxial electrospray of uniform polylactide core-shell microparticles for long-acting contraceptive

Despite its high efficacy and good patient compliance, the only long-acting injectable (LAI) contraceptive currently available in the US, depot medroxyprogesterone acetate (DMPA), is limited by significant side effects and a delayed return to fertility for up to 10 months after its intended duration of action. To overcome these limitations, we sought to develop an injectable poly(D,L-lactide) (PLA) microparticle for sustained release of contraceptive hormone, etonogestrel (ENG). A one-step technique, coaxial electrospray method was applied to prepare uniform ENG loaded core-shell structured and slow-degrading PLA microparticles (ENG-cs-MPs) to provide release control while minimizing polymer content. By adjusting voltage, polymer concentration and flow rate of the coaxial jetting solution, the prepared ENG-cs-MPs exhibited uniformly small particle size with volume mean diameter of 14.7 +/- 0.5 mu m and a shell thickness of 2.5 +/- 0.1 mu m, high drug loading of -54%, high encapsulation efficiency of -99%, and initial 1-day burst release of just -10%. Long-term in vitro release of ENG was continuous for more than 3 months without change of the shell structure in 6 months. In PK studies, ENG-csMPs achieved a steady and continuous drug release for approximately 3 months and then quickly tapered off within 3 weeks. Hence, ENG-cs-MPs prepared by the coaxial electrospray method may be useful as a LAI contraceptive with an improved PK profile relative to DMPA.

Automated summary

This study aimed to develop an injectable poly(D,L-lactide) (PLA) microparticle for sustained release of contraceptive hormone, etonogestrel (ENG). The ENG-cs-MPs prepared by the coaxial electrospray method showed high drug loading, high encapsulation efficiency, and long-term stable release, suggesting their potential as a long-acting injectable contraceptive with improved pharmacokinetic profile.