Nanoparticle-Assisted Combinatorial Therapy for Effective Treatment of Endometriosis

Endometriosis is characterized by the presence of endometrial glands and stroma outside the uterine cavity. Conventional treatment modalities for endometriosis are unsatisfactory; therefore, there is a need to treat the underlying causes and mechanism. Oxidative stress, extracellular matrix degradation, and angiogenesis are associated with the pathogenesis of endometriosis. The anti-angiogenic and antioxidant properties of epigallocatechin gallate and the matrix metalloproteinase inhibitory activity of the antibiotic doxycycline are well established. However, epigallocatechin gallate and doxycycline have several limitations when used in their native forms. This motivated us to synthesize dual drug-loaded (epigallocatechin gallate and doxycycline) nanoparticles and check their therapeutic efficacy in mice with induced endometriosis. The synthesized nanoparticles displayed features of a promising drug-delivery system, such as small size, high encapsulation efficiency, controlled drug release, and low toxicity. The serum of endometriosis-induced mice and controls was assessed for various oxidative stress markers, matrix-degrading enzymes, and angiogenic markers before and after nanoparticle administration. Endometrial glands, stroma, and new microvessels were determined using histochemistry and immunohistochemistry. Treatment with dual drug-loaded nanoparticles markedly decreased oxidative stress, matrix metalloproteinase activity, and angiogenesis, as well as endometrial gland presence and microvessel density. Mitigation of endometriosis-related adverse effects further produced an improvement in the quality of oocytes, which is critical for successful pregnancy outcomes. Our observations suggest that owing to their combinatorial effect, poly(lactic-co-glycolic) acid nanoparticles loaded with epigallocatechin gallate and doxycycline in a single vehicle appear to be promising for the treatment of endometriosis.