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

Abstract

Mazhar Ali Raja,1,2 Martin Maldonado,2 Jianying Chen,2 Ying Zhong,2 Jiang Gu1,2 1Laboratory of Molecular Pathology, Provincial Key Laboratory of Infectious Diseases and Molecular Pathology, Center of Molecular Diagnosis and Personalized Medicine, Shantou University Medical College, Shantou, People’s Republic of China; 2Chengdu Jinxin Research Institute for Reproductive Medicine and Genetics, Reproductive Center of Chengdu Jinjiang District Maternal and Child Health Hospital, Chengdu, People’s Republic of ChinaCorrespondence: Jiang GuLaboratory of Molecular Pathology, Provincial Key Laboratory of Infectious Diseases and Molecular Pathology, Center of Molecular Diagnosis and Personalized Medicine, Shantou University Medical College, Xinling Road 22, Shantou, Guangdong, 515041, People’s Republic of ChinaEmail [email protected]; [email protected] ZhongChengdu Jinxin Research Institute for ReproductiveMedicine and Genetics, ReproductiveCenter of Chengdu Jinjiang District Maternal and Child Health Hospital, No. 66, 88 Bi Sheng Road, Chengdu, 610023, People’s Republic of ChinaEmail [email protected]: 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.Keywords: polycystic ovary syndrome, curcumin, self-assembled nanoparticles, cytotoxicity, cellular uptake

Keywords

• polycystic ovary syndrome
• curcumin
• self- assembled nanoparticles
• cytotoxicity
• cellular uptake