Development and Evaluation of Curcumin Encapsulated Self-assembled Nanoparticles as Potential Remedial Treatment for PCOS in a Female Rat Model

Abstract

Purpose Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies affecting women of reproductive age and leads to metabolic disorders and infertility. The present study was conducted to investigate the therapeutic effects of curcumin (Cur) encapsulated arginine (Arg) and N-acetyl histidine (NAcHis) modified chitosan (Arg-CS-NAcHis/Cur) nanoparticles (NPs). Methods In this study, amphiphilic chitosan (CS) conjugate was developed by modification with hydrophilic arginine (Arg) and hydrophobic N-acetyl histidine (NAcHis) group (Arg-CS-NAcHis). The synthesized conjugate was well characterized by FTIR and NMR studies. Self-assembled nanoparticles based on the synthesized conjugate were developed by simple sonication method and characterized for the physicochemical properties of zeta potential, particle size and drug encapsulation. Next, in vitro drug release, cytotoxicity, and cellular uptake studies of the NPs were evaluated. Finally, the developed nanoparticles were examined for their therapeutic potential against estradiol valerate (EV) induced PCOS rats by evaluating hormone level changes and ovarian morphology. Results The results showed that zeta potential of the nanoparticles was 39.8±2.52 mV and the average size was 200 nm. The in vitro drug release profile showed sustained release pattern. Cytotoxicity and cellular uptake studies also showed preferential effectiveness than free curcumin. Both the biochemical and histopathological studies showed positive effects in reverting the symptoms of PCOS rats to normalcy. Conclusion Curcumin encapsulated arginine and N-acetyl histidine modified chitosan (Arg-CS-NAcHis/Cur) nanoparticles have been successfully developed. The present study suggested that treatment of the nanoparticles might reverse many of the PCOS symptoms. Therefore, these nanoparticles might be used as promising new candidate for delivery of curcumin to treat PCOS.

Curcumin Inhibits Hyperandrogen-Induced IRE1α-XBP1 Pathway Activation by Activating the PI3K/AKT Signaling in Ovarian Granulosa Cells of PCOS Model Rats

“…In a randomized double-blind placebo-controlled trial, individuals with PCOS were treated with curcumin (500 mg, three times daily) for 12 weeks. The results showed that curcumin significantly reduced the amount of DHEA and might even increase estradiol levels in women with PCOS [ 37 ]. Another report showed that treatment with curcumin-encapsulated arginine and N-acetyl histidine-modified chitosan (Arg-CS-NAcHis/Cur) nanoparticles reversed many symptoms of PCOS [ 37 ].…”

“…The results showed that curcumin significantly reduced the amount of DHEA and might even increase estradiol levels in women with PCOS [ 37 ]. Another report showed that treatment with curcumin-encapsulated arginine and N-acetyl histidine-modified chitosan (Arg-CS-NAcHis/Cur) nanoparticles reversed many symptoms of PCOS [ 37 ]. Our study showed that curcumin protected ovarian GCs from hyperandrogen-induced apoptosis in PCOS model rats probably by inhibiting the IRE1 α -XBP1 levels and activating the PI3K/AKT signaling pathway.…”

The Efficacy of Chinese Herbal Medicine in Animal Models of Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis

“…As another androgen induction method, DHEA and prasterone sulfate sodium require shorter modeling time than testosterone propionate and are closer to the pathogenesis of PCOS [ 45 , 46 ]. In addition to the modeling methods mentioned in this study, estradiol valerate, insulin combined with human chorionic gonadotrophin (HCG), and progesterone combined with HCG have also been used in other studies to induce PCOS models [ 47 – 49 ]. There were also studies modeling PCOS through torsion-detorsion and found that apoptosis caused by oxidative stress is an important factor in ovarian tissue damage [ 50 ].…”

Natural Products and Nanotechnology Against Coronavirus Disease 2019

“…The amalgamation of novel drug delivery nanocarriers with drug complexes can effectively eliminate the molecular limitations of their entry into the body ( Nabi et al, 2019 ). By using nanocarriers such as nanoparticles, nanoliposomes, and alcohol solutes, natural products can be loaded and smoothly inserted into the appropriate parts of the body ( Allaw et al, 2020 ; Raja et al, 2021 ; Salarbashi et al, 2021 ). On the one hand, nanotechnology increases the solubility of a low soluble compound and improves its stability, however, nanotechnology can be combined to enhance the effectiveness of the therapeutic drug and reduce its side effects ( Kaur et al, 2021 ) ( Figures 2 and 3 ).…”