Letrozole and Curcumin Loaded-PLGA Nanoparticles: A Therapeutic Strategy for Endometriosis

Abstract

Clinical treatment of endometriosis, a common gynaecological disorder, still remains a challenge. Hormonal suppression, pain relief medication and surgical intervention are the conventional treatment modalities; however, frequent recurrence of the disease renders the results unsatisfactory. Given the fact that oxidative stress, angiogenesis, excessive matrix degradation, and aromatase activity are associated with endometriosis, we were motivated to use the combinatorial effect of two drugs, Curcumin (Cur) and Letrozole (Let) encapsulated in PLGA and test their efficacy in mice induced with the disease. The nanoparticles (NPs) were synthesized using solvent evaporation method and characterization indicated the spherical particles to be monodispersed, polymorphic, small in size with high encapsulation efficiency, without having a tendency for significant aggregation or adhesion. Following standardization, 40mg/kg body weight of NPs was administered in endometriotic mice. Oxidative stress parameters, angiogenic markers, matrix degrading molecules, estrogen levels and endometriotic lesions, were assessed and compared before and after administration. Let-Cur NPs treatment in vivo, in addition to decreasing these parameters significantly, was also successful in reducing endometrial glands and micro-vessels density in the peritoneum to a considerable extent, thereby indicating significant regression of the disease. This is a proof of concept study. Pre-clinical non-human primate studies for testing the safety and efficacy of these NPs at larger doses in endometriosis is suggested. Citation: Jana SK, Chakravarty B, Chaudhury K (2014) Letrozole and Curcumin Loaded-PLGA Nanoparticles: A Therapeutic Strategy for Endometriosis.

Curcumin and Endometriosis

“…Inflammation Nx rats Reduction of NF-kappaB [102] Rat liver TNF-α, COX-2, IL-6 and TGF-beta [103] Mice macrophages NF-κB pathway, TNF-α, IL-1, IL-6, and IL-8 [104,105] Human eutopic endometrial stromal cells chemokines, cytokines and NF-κB pathway [113] Human myeloid ML-1a cells Blockage of I-κB phosphorylation [106] Intestinal epithelial cells the inactivation of I-κB kinase complex [107] Oxidative stress Mice Reduction of ROS serum and lipid peroxidation [114] Mice Lipid peroxidation and protein oxidation [115] Nx rats Regulation of NrF2-Keap1 [102] Mice macrophages Diminution of NO synthase expression [116] lymphocytes Increase of glutathione and superoxide dismutase [117]…”

“…In endometriosis, there are few reports on the role of curcumin in OS. Nevertheless, administration of Letrozole-curcumin has been associated with a reduction of ROS serum and lipid peroxidation in mice [114]. Moreover, therapy by curcumin in endometriosis mice can prevent against lipid peroxidation and protein oxidation [115].…”

Specific Photothermal Ablation Therapy of Endometriosis by Targeting Delivery of Gold Nanospheres

“…Polymeric micelles compressing Pigment epithelium derived factor (PEDF) plasmid were used to treat endometriosis by suppressing angiogenesis . In another study, curcumin and letrozole were encapsulated in poly(lactic‐co‐glycolic acid) (PLGA) nanoparticles, and their efficacy in treating the disease was tested . However, these studies had limited therapeutic efficiency against endometriosis because of the lack of specific treatment and the potential systemic toxicity.…”

Preparation and optimization of monodisperse polymeric microparticles using modified vibrating orifice aerosol generator for controlled delivery of letrozole in breast cancer therapy

“…exceeding 80% of the drug originally loaded). The higher burst release has been ascribed to the polydispersity of particles prepared in those studies and the fact that these were nanoparticles with higher surface area [11,54]. Thus, our microparticles generated using the VOAG technology represent and advancement with a considerable advantage since the potential adverse effects that may occur due to the overwhelming burst effect would be diminished.…”