RECENT ADVANCES IN SUSTAINED RELEASE DRUG DELIVERY SYSTEMS FOR ENDOMETRIOSIS THERAPY

Rajat Rai*, Manju Makhija

ABSTRACT

Endometriosis affects 10–15% of reproductive-aged women, yet current therapies remain largely palliative and non-curative. Hormonal treatments (oral contraceptives, progestins, GnRH agonists/antagonists) suppress ovulation and menstruation but do not eliminate ectopic lesions, cause significant systemic side effects, and are associated with 50–80% pain recurrence within six months of discontinuation. Surgical excision, while effective for pain and fertility, is limited by incomplete resection, operative risks, and 40–50% five-year recurrence rates. The central unmet need is the inability to achieve sustained, high local drug concentrations within endometriotic lesions without systemic toxicity. This review critically examines recent advances in sustained release drug delivery systems designed to overcome these barriers. Lipid-based nanocarriers—nanostructured lipid carriers (NLCs), solid lipid nanoparticles (SLNs), and nanoemulsions—exploit the enhanced permeability and retention (EPR) effect of lesion vasculature, achieving prolonged drug release and reduced systemic exposure. NLC-encapsulated mifepristone provides 21-day sustained release in preclinical models, reducing lesion volume by 82%. Polymeric nanoparticles, particularly PLGA and chitosan-based systems, enable tunable degradation kinetics and gene silencing (e.g., VEGF siRNA with 70% mRNA knockdown). Hyaluronic acid-functionalized nanocarriers actively target CD44-overexpressing lesions, improving drug accumulation 2.5 to 8 fold. Injectable and in situ forming hydrogels—including photothermal/endocrine synergistic systems (LTZ-PDA@AG), thermoresponsive mucoadhesive poloxamer gels, and NIR-controlled microspheres—offer localized, stimuli-responsive therapy with lesion volume reductions up to 92% in animal models. Next-generation intrauterine drug delivery systems (IUDDS), such as biodegradable WOMED platforms and photo crosslinkable implants, eliminate the need for device removal while providing ultra-long-acting levonorgestrel release. Despite these promising preclinical advances, clinical translation remains nascent, with only a single pilot trial (LDE-MTX) reported to date. Major challenges include overcoming the dense fibrotic barrier of deep infiltrating lesions, scalable GMP manufacturing, reproductive safety validation, and regulatory navigation for drug-device combination products. The convergence of nanomedicine, image-guided theranostics, and molecular phenotyping promises a future of personalized, fertility-preserving, locally administered therapies that move beyond episodic suppression to chronic disease modification.

Keywords: Endometriosis; sustained release drug delivery; lipid nanoparticles; polymeric nanoparticles; hydrogels; intrauterine drug delivery systems; non-hormonal therapy; active targeting; CD44; photothermal therapy; fibrosis; anti-angiogenic agents; clinical tra