Thermosensitive hydrogels a versatile concept adapted to vaginal drug delivery

Abstract

Vaginal drug delivery represents an attractive strategy for local and systemic delivery of drugs otherwise poorly absorbed after oral administration. The rather dense vascular network, mucus permeability and the physiological phenomenon of the uterine first-pass effect can all be exploited for therapeutic benefit. However, several physiological factors such as an acidic pH, constant secretion, and turnover of mucus as well as varying thickness of the vaginal epithelium can impact sustained drug delivery. In recent years, polymers have been designed to tackle challenges mentioned above. In particular, thermosensitive hydrogels hold great promise due to their stability, biocompatibility, adhesion properties and adjustable drug release kinetics. Here, we discuss the physiological and anatomical uniqueness of the vaginal environment and how it impacts the safe and efficient vaginal delivery and also reviewed several thermosensitive hydrogels deemed suitable for vaginal drug delivery by addressing specific characteristics, which are essential to engage the vaginal environment successfully.

Keywords:

• Female reproductive system
• gynaecology
• drug delivery
• uterine first pass effect
• lower critical solution temperature
• gelation
• biocompatibility
• mucoadhesion
• viscosity
• pluronics

Acknowledgements

The authors would like to thank Shirley Reyes for her graphical contributions, Zachary Clauss for proof-reading and discussions, Prof. Kang Moo Huh and Dr. Sungpil Cho for their guidance and collaboration throughout Dr. Aliyah Almomen’s graduate studies.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the National Cancer Institute (1R01CA140348-01), the University of Utah’s Vice President’s Office of Research Seed Funding as well as the Department of Obstetrics and Gynecology.