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

Jie Tang; Richard Schutzman; Carlos A Rodríguez; Joerg Lahann; Naír Rodríguez-Hornedo; Mark R Prausnitz; Steven P Schwendeman

doi:10.1016/j.jconrel.2021.12.017

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

J Control Release. 2022 Jan:341:634-645. doi: 10.1016/j.jconrel.2021.12.017. Epub 2021 Dec 16.

Authors

Jie Tang¹, Richard Schutzman², Carlos A Rodríguez³, Joerg Lahann⁴, Naír Rodríguez-Hornedo³, Mark R Prausnitz⁵, Steven P Schwendeman⁶

Affiliations

¹ Department of Pharmaceutical Sciences, University of Michigan, 428 Church Street, Ann Arbor, MI 48109, USA; The Biointerfaces Institute, University of Michigan, North Campus Research Complex, 2800 Plymouth Road, Ann Arbor, MI 48109, USA. Electronic address: tangjie@umich.edu.
² Department of Pharmaceutical Sciences, University of Michigan, 428 Church Street, Ann Arbor, MI 48109, USA; The Biointerfaces Institute, University of Michigan, North Campus Research Complex, 2800 Plymouth Road, Ann Arbor, MI 48109, USA.
³ Department of Pharmaceutical Sciences, University of Michigan, 428 Church Street, Ann Arbor, MI 48109, USA.
⁴ The Biointerfaces Institute, University of Michigan, North Campus Research Complex, 2800 Plymouth Road, Ann Arbor, MI 48109, USA; Department of Biomedical Engineering, University of Michigan, 2200 Bonisteel Blvd, Ann Arbor, MI 48109, USA; Department of Chemical Engineering, University of Michigan, 2300 Hayward St, Ann Arbor, MI 48109, USA.
⁵ School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, 311 Ferst Drive, Atlanta, GA 30332, USA.
⁶ Department of Pharmaceutical Sciences, University of Michigan, 428 Church Street, Ann Arbor, MI 48109, USA; The Biointerfaces Institute, University of Michigan, North Campus Research Complex, 2800 Plymouth Road, Ann Arbor, MI 48109, USA; Department of Biomedical Engineering, University of Michigan, 2200 Bonisteel Blvd, Ann Arbor, MI 48109, USA. Electronic address: schwende@umich.edu.

PMID: 34921972
DOI: 10.1016/j.jconrel.2021.12.017

Abstract

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 μm and a shell thickness of 2.5 ± 0.1 μm, 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-cs-MPs 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.

Keywords: Coaxial electrospray; Core-shell structure; Long-acting injectable contraceptives; Microparticles; Polylactide; Sustained release.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Contraceptive Agents*
Drug Liberation
Humans
Particle Size
Polyesters* / chemistry

Substances

Contraceptive Agents
Polyesters
poly(lactide)