Developing Therapeutic Poly(caprolactone) Nanoparticles for Endometrial Drug Delivery Applications (Emerging Themes for Research: Nanomedicine and Bioelectronics Research Center)

Diseases of the endometrium are the leading causes of gynecological diseases in women worldwide. Recently, researchers highlighted the lack of funding towards women’s health, which represents a critical challenge in advancing the quality of healthcare.1, 2 Oftentimes, the recommended treatment for endometrial disease is a partial or total hysterectomy, which can be invasive and only partially successful at reducing long-term symptoms and disease progression. Surgical options are particularly challenging for high-risk patients and those still within reproductive age, who do not want to limit their fertility options. Hormone therapies have been used in place of surgery, although with inconsistent results. This highlights a critical need for innovative treatment strategies to effectively treat gynecological diseases affecting endometrial tissue. Nanoparticle therapeutics are promising drug delivery strategies because nanoparticles are highly versatile. Given their small size and scientifically controlling for desired surface properties, nanoparticles can enter cells via passive diffusion to effectively deliver drugs and other small molecules that otherwise would not readily enter cells. Polymeric particles are also advantageous as drug delivery carriers because they can encapsulate hydrophilic or hydrophobic drugs, have a tailorable size, and undergo post-processing to add surface modifications that improve targeting.3-6 Many of these nanoparticles are produced using biocompatible and biodegradable polymers that have been FDA-approved, including poly(lactic acid), poly(glycolic acid), poly(lacticco-glycolic acid), poly(hydroxy alkanoates), poly(ethylene glycol), and poly(caprolactone).7 In this study, we will use poly(caprolactone), PCL, which is a biocompatible and biodegradable polyester capable of forming nanoand micro-particles. PCL slowly degrades via hydrolysis and thus provides an opportunity for us to develop a nanoparticle formulation appropriate for systemic delivery. To evaluate the efficacy of the proposed construct, we will characterize the particle surface chemistry and use this to explain the observed endometrial cellular responses. Furthermore, we will quantify the pH-dependent kinetics of particle drug release at physiological and vaginal pH.