2024 AIChE Annual Meeting

Hydrogels with Microsphere Drug Delivery Technology to Promote Healing Post-Pelvic Radiotherapy and Prevent Vaginal Stenosis

Women’s healthcare is often underfunded and overlooked, contributing to suboptimal outcomes in treating conditions such as gynecological cancers. In 2023 alone, there were 114,810 new cases1 of gynecological cancer and about 60% received radiotherapy as treatment2. As a side effect of radiotherapy, approximately half of these patients3 will experience vaginal adhesions and stenosis, which is the formation of scar tissue, causing patient discomfort with exams, poor vaginal health, and limiting sexual function. Use of current solutions, like vaginal dilators or topical treatments, are limited in the immediate post-radiation timeframe when the primary injury response occurs, because of patient discomfort. To address this issue, an injectable bioadhesive hydrogel was created to prevent post-radiation damage in the vaginal canal by keeping the injured tissue apart. This bioadhesive, based on crosslinked polyethylene glycol, offers a protective, physical barrier to reduce vaginal adhesions and stenosis. Additionally, the hydrogel contains polylactic-co-glycolic acid microspheres (PLGA-MS) loaded with estradiol (E2) to help promote the healing of the tissue and reepithelization of the vaginal mucosa.

The polymers chosen in this study provide properties that allow the gel to adhere to tissue and have tunable gelation kinetics for easy injectability. To optimize the formulation of the gels for the treatment of vaginal toxicity, the gels must be mechanically characterized, easily injectable, bioadhesive, and compatible with a controlled drug delivery system.

To meet these criteria, tests were performed regarding gelation kinetics of the PEG-based bioadhesive, the size of the PLGA-MS, and loading efficiency of the PLGA-MS. Rheometric analysis was done using ASTM D2556 to determine gelation kinetics. The bioadhesive solutions (n=4 per formulation) were casted onto the rheometer to undergo polymerization while the test was being run at 37 oC. Preliminary bioadhesive testing was done using mice skin tissues. The hydrogels were cast on the tissue after being soaked in 1X PBS and visual inspection confirmed strong bioadhesion. To assess the feasibility of incorporating PLGA-MS into the hydrogels, the spheres were prepared using a single emulsion technique and imaged under a microscope. ImageJ was used to analyze the size and distribution of the spheres. This resulted in an average particle size of 45-50 microns, suitable for embedding in the bioadhesives during polymerization. High-performance liquid chromatography of the loaded E2 PLGA-MS was done using an Avantor C18 column. Standard curves of E2 in acetonitrile were created using a mobile phase of water/acetonitrile 40:60. After placing the microspheres in acetonitrile (varying concentrations of E2 mg/mL), the loading efficiency was determined to be 87.2%. Further studies aim to optimize the gel formulation and study the controlled release of E2-loaded PLGA-MS embedded in the hydrogels.

References

  1. Gynecological cancers - Foundation for Women’s Cancer. Foundation For Women’s Cancer - Eradicate or lessen the impact of gynecologic cancer. (2024, August 21). https://foundationforwomenscancer.org/gynecological-cancers/
  2. Karlsson, J. A., & Andersen, B. L. (1986). Radiation therapy and psychological distress in gynecologic oncology patients: Outcomes and recommendations for enhancing adjustment. Journal of psychosomatic obstetrics and gynaecology. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2763444/#:~:text=Of%20the%…
  3. Varytė, G., & Bartkevičienė, D. (2021, April 1). Pelvic radiation therapy induced vaginal stenosis: A review of current modalities and recent treatment advances. Medicina (Kaunas, Lithuania). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066324/