Nanoparticle

Materials science

Chromatography

Controlled release

Core (optical fiber)

Environmental health

Polymer

Nanotechnology

Family planning

Levonorgestrel

Transdermal

Shell (structure)

Population

Pharmacology

Composite material

Medicine

Chemistry

PLGA

Transdermal patch

Research methodology

Biodegradable polymer

Dosage form

Journal of Controlled Release

There is a tremendous need for simple-to-administer, long-acting contraception, which can increase access to improved family planning. Microneedle (MN) patches enable simple self-administration and have previously been formulated for 1-2 months' controlled release of contraceptive hormone using monolithic polymer/drug MN designs having first-order release kinetics. To achieve zero-order release, we developed a novel core-shell MN patch where the shell acts as a rate-controlling membrane to delay release of a contraceptive hormone, levonorgestrel (LNG), for 6 months. In this approach, LNG was encapsulated in a poly(lactide-co-glycolide) (PLGA) core surrounded by a poly(l-lactide) (PLLA) shell and a poly(D,L-lactide) (PLA) cap that were fabricated by sequential casting into a MN mold. Upon application to skin, the core-shell MNs utilized an effervescent interface to separate from the patch backing within 1 min. The core-shell design limited the initial 24 h burst release of LNG to 5.8 ± 0.5% and achieved roughly zero-order LNG release for 6.2 ± 0.1 months in vitro. A monolithic MN patch formulated with the same LNG and PLGA core, but without the rate-controlling PLLA shell and PLA cap had a larger LNG burst release of 22.6 ± 2.0% and achieved LNG release for just 2.1 ± 0.2 months. This study provides the first core-shell MN patch for controlled months-long drug release and supports the development of long-acting contraception using a simple-to-administer, twice-per-year MN patch.

Core-shell microneedle patch for six-month controlled-release contraceptive delivery