Design and evaluation of a novel nanodrug delivery system for reducing the side effects of clomiphene citrate on endometrium

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. ResultsThe 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 PBFtreated 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.

Sperm–oviduct interaction: Differential gene expression of growth factors induced by sperm DNA fragmentation

“…The calculation of relative expression was performed based on the double‐delta Ct method (Ajdary et al, 2020). According to the study samples and the genes of interest, ACTB and GAPDH were selected as reference genes by Norm‐Finder analysis.…”

The effect of vitamin D3 provided with Phytosolve on the genes involved in implantation in the PCOS model

“…Integrins exhibit a sandwich-like structure in the embryonic junction ( Wang & Armant, 2002 ; Achache & Revel, 2006 ; Jiang & Li, 2022 ; Zhang et al ., 2022; Bajpai et al ., 2023 ). Additionally, expression of LIF mRNA in the endometrium of healthy women occurs during the middle and late secretory phases of the menstrual cycle, as well as in early pregnancy ( Aghajanova, 2004 ; Kara et al ., 2016 ; Ajdary et al ., 2020 ; Fukui et al ., 2022 ; Bajpai et al ., 2023 ). The HOXA-10 gene also has a physiological role in implantation by regulating the response of endometrial stromal cells to progesterone ( Celik et al ., 2015 ; Kara et al ., 2016 ; 2019 ; Zhang et al , 2022; Bajpai et al ., 2023 ).…”

Formulation and Characterization of Poly (Acrylic Acid)- Co-Chitosan Nanoparticles as pH-Thermo-Responsive System to Control Delivery

“…Chitosan is a hydrophilic, cationic polymer with great biocompatibility and high drug loading efficiency. Several studies improved its pH and thermo-sensitivity [17,18]. However, its limited application to controlled drug delivery and its insolubility [19] make its complexation with another polymer necessary to improve its physico-chemical properties and consequently obtain a desire nanoparticle.…”