Fabrication of controlled-release polymeric microneedles containing progesterone-loaded self-microemulsions for transdermal delivery

Abstract

Progesterone (PG) has been approved for hormone replacement therapy to mitigate the risk of endometrial carcinoma. However, there has been a lack of success in oral PG due to its rapid degradation. Transdermal PG has advantages but lacks efficacy due to its poor solubility (Log p = 3.9). Therefore, this study aimed to evaluate how combining self-microemulsifying drug delivery systems (SMEDDS) and polymeric microneedles (MNs) could improve the transdermal delivery of PG in a controlled-release manner. Among PG-SMEDDS, PG–SME5 was selected for its desirable properties and stability. The two-layer polymeric MNs formulation incorporating PG–SME5 (PG-SMEDDS-tMNs) was formulated from aqueous blends of polymers as a first layer and 20% PCL as a second layer. It successfully penetrated neonatal porcine skin with the dissolution of the first layer observed within 15 min after application. In vitro skin permeation revealed that the percentage of PG which permeated the skin over 82 h using PG-SMEDDS-tMNs was higher than a PG-suspension and PG-SMEDDS. The Higuchi kinetic showed controlled release over 15 days of PG from PG-SMEDDS-tMNs. These studies suggested that incorporating PG-SMEDDS into controlled-release two-layer polymeric MNs could be a promising approach for improving the transdermal delivery of PG.

Graphical Abstract

Keywords:

• Control release microneedles
• self-microemulsifying drug delivery system
• progesterone
• transdermal drug delivery

Acknowledgments

This research was supported by Silpakorn University under the Postdoctoral fellowship program.

Authors’ contributions

Phuvamin Suriyaamporn: software, formal analysis, investigation, data curation, and writing-original draft preparation. Porawan Aumklad: formal analysis, investigation, and writing-original draft preparation. Theerasak Rojanarata: method validation. Prasopchai Patrojanasophon: methodology and statistical analysis. Tanasait Ngawhirunpat: methodology. Boonnada Pamornpathomkul: conceptualization, project administration, visualization, proofreading, and editing. Praneet Opanasopit: conceptualization, supervision, resources, and funding acquisition. All authors have read and agreed to the published version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This research was supported by Silpakorn University under the Postdoctoral fellowship program.