(66a) Division 15 Plenary Award - Development of a Microneedle Patch for Long-Acting Contraception

With approximately 40% of pregnancies worldwide being unplanned, there is an urgent need for improved methods of contraception. The most-effective contraceptives are those which are long-acting, since they do not require user compliance on a daily basis or at the time of intercourse. However, long-acting contraceptives generally require expert administration, such as injection or implantation. This not only adds cost and inconvenience, but can be a major barrier to contraceptive access in places with limited health care resources. In some culture, discreetness of contraception is also important due to pressures from partners, family and the community.

We therefore set out to develop a contraceptive that is long-acting (to improve efficacy), self-administered (to improve access) and discreet (to improve acceptability). Our approach involves a microneedle patch that slowly releases the well-established contraceptive hormone, levonorgestrel (LNG). These patches have an array of solid, conical microneedles measuring hundreds of microns in length and loaded with drug that painlessly penetrate into the skin after pressing the patch to the skin. Microneedle patches are widely used for cosmetic applications like anti-aging, and have been in numerous clinical trials for bolus delivery of drugs and vaccines using microneedles made of rapidly water-soluble materials.

In our research, we are extending microneedle technology in a number of ways to achieve the goal of a discreet, self-administered, long-acting contraceptive. A notable advance has been transitioning from water-based formulations and organic solvent-based formulations needed to solubilize the LNG and biodegradable polymers used to achieve slow drug release. The microneedle patch fabrication process involves casting a first formulation onto a micromold of the microneedle patch to fill the microneedle cavities with LNG and polymer, which is either poly(lactic acid) (PLA) and/or poly(lactic-co-glycolic acid) (PLGA) in an organic solvent. A second cast of water-soluble excipients like poly(vinyl alcohol) and sucrose in water forms the backing layer of the patch. Upon drying, this yields a microneedle patch that deposits microneedles in the skin for slow release of LNG from the biodegradable polymer matrix, and does so discreetly because the water-soluble patch backing separates from the microneedles upon contacting the aqueous fluids of the skin, leaving behind no evidence of the microneedles on the skin surface. In addition to dissolution-based separation of the microneedles from the patch backing, we have also developed methods based on mechanical fracture by incorporating porosity and based on effervescence by incorporating effervescent materials at the microneedle-backing interface.

Using this approach, we have been able to develop microneedle patches that achieve one-month and six-month release periods in vitro, and have demonstrated the one-month release profiles in vivo in rats as well; the six-month release studies in vivo are pending. The microneedles are strong enough to insert into skin, and are generally reported to be painless by human subjects. Efforts are underway to develop the long-acting contraceptive microneedle patch for human clinical trials that can lead to their future use in clinical medicine and public health.