Development of nanoparticles loaded in-situ gels as regional vaginal, uterine and pelvic depots for treatment of endometriosis

Problem statement: Endometriosis is a health disorder in which tissue similar to the endometrial walls inside
the uterus grows outside the uterus. It is a long-standing challenge affecting women and is associated with
pain and infertility, affecting 176 million reproductive-age women worldwide, including 26 million Indian
women. The current therapies have systemic adverse effects that affect fertility and with high chances of
disease recurrence. Recently letrozole drug has been used orally for the treatment of endometriosis but has
a high incidence of osteoporosis. We aim to develop letrozole-loaded nanoparticles incorporated in situ gels
as depots for regional delivery for uterine, vaginal and laparoscopic pelvic instillation. This technology will
benefit reproductive-age women, suffering from endometriosis and will be a boon for infertile females who
are unable to conceive because of ectopic growth of the endometrium. Such technology will be essential for
the improvement of women's health by treating endometriosis regionally in a patient-compliant manner
with minimal systemic side effects. Once a platform technology is developed, it can also be explored for

other uterine conditions. It is a novel drug delivery that will address the unmet medical needs of non-
hormonal regional treatment and could be used in all stages of endometriosis in women of all ages.

Project details: This project aims to develop a letrozole-drug-loaded nanoparticle formulation for the
treatment of endometriosis. This formulation can gel in vivo and form a bio-adherent lining forming regional
drug depots (as vaginal, intrauterine, and laparoscopic pelvic delivery) with prolonged and trigger-responsive
regional delivery of over a month. The specific aims of this project are:

• Development and optimization of letrozole loaded nanoparticles, degradable in situ gels, and nanoparticle in in-situ gel formulations
• Evaluation of the effect of formulation on inflammation and invasion of endometrial cells in vitro
• Evaluation of the stability of optimized formulations in accordance with ICH guidelines
• Evaluate pharmacokinetics, retention, and biodistribution of developed formulation when administered through vaginal, intrauterine, and pelvic routes in comparison with conventional oral letrozole

The proposed delivery system will release letrozole as per the severity of the condition as they will be trigger
responsive to the matrix metalloprotease levels (A member of a group of enzymes that can break down
proteins) and will be biodegradable. It is expected to reduce systemic toxicity while enhancing pelvic drug
levels which are the commonly affected sites. This will provide a novel drug delivery that will address the
unmet medical need of a non-hormonal regional treatment without systemic side effects that can be used
in all stages of endometriosis in women of all ages. This treatment method is expected to reduce systemic
toxicity while enhancing pelvic drug levels. The project will lead to novel drug delivery for endometriosis.
We aim to optimize the product for self-administration vaginally, as well as catheter-based uterine instillation
and laparoscopic administration for advanced endometriosis. The versatility of the technology will allow us
to address all stages of endometriosis in accordance with the revised scoring system of the American Society
of Reproductive Medicine.