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Design and Evaluation of a Novel Nanodrug Delivery System for Reducing the Side Effects of Clomiphene Citrate on Endometrium Publisher Pubmed



Ajdary M1 ; Keyhanfar F2 ; Aflatoonian R3 ; Amani A4, 5 ; Amjadi FS6 ; Zandieh Z6 ; Mehdizadeh M1, 6
Authors
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Authors Affiliations
  1. 1. Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
  4. 4. Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran
  5. 5. Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Department of Anatomical Science, Iran University of Medical Sciences, Tehran, Iran

Source: DARU# Journal of Pharmaceutical Sciences Published:2020


Abstract

Background: Stimulation of ovulation with clomiphene citrate can cause side effects on endometrial receptivity. Formulation with nano-size may be an alternative therapy for women with ovulatory disorders. In this study, we investigated sustained-release clomiphene citrate by using Phosal-based formulation (PBF) and evaluate its decreased side effect on the endometrial receptivity. Methods: In the in-vitro study, CC loaded PBF was analyzed using Zetasizer, Fourier-transform infrared spectroscopy (FTIR), and Transmission electron microscopy (TEM). In the in-vivo study, 24 female mice were randomly divided into three groups: CC (5 mg/kg), CC/PBF (5 mg/kg) and SS (1 ml) daily administered and injected with 5 IU HCG and mated after two days. At day 4.5, pregnant mice were euthanized and endometrial tissue was extracted for quantitative polymerase chain reaction (Q-PCR) analysis. Results: The optimized PBF contained Phosal 50PG/glycerol in a 2:8 ratios (w/w) and the particle size of optimum formulation was 67 ± 0.30551 nm and the release of CC from CC-containing PBF was slightly faster in the first 24 h; wherein, 29% of CC was released, and 76% of CC was released up to 120 h. The mRNA levels of leukemia inhibitory factor (LIF), leukemia inhibitory factor receptor alpha (LIFR), HOXA10, Heparin-binding epidermal growth factor (HB-EGF), and epidermal growth factor (EGF) were significantly upregulated and MUC1 and PGR mRNA levels were significantly downregulated in the CC-containing PBF-treated animals compared with only CC group (P < 0.05). Conclusion: Sustained release formulation of clomiphene citrate increased its targeting efficiency and improved the impact of the CC on implantation. [Figure not available: see fulltext.] © 2019, Springer Nature Switzerland AG.