Design and evaluation of a novel nanodrug delivery system for reducing the side effects of clomiphene citrate on endometrium
DARU-JOURNAL OF PHARMACEUTICAL SCIENCES
Authors: Ajdary, Marziyeh; Keyhanfar, Fariborz; Aflatoonian, Reza; Amam, Amir; Amjadi, FatemehSadat; Zandieh, Zahra; Mehdizadeh, Mehdi
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. Graphical abstract A new Phosal Based Formulation (PBF) was designed to decrease the side effects of Clomiphene citrate (CC) on endometrium. This drug formulation could react better during implantation by increasing the expression of genes involved in implantation. The in vivo study demonstrated that the CC-containing PBF in mice has a significantly higher endometrial receptivity, compared with the suspension.
Impact of Different Phytohormones on Morphology, Yield and Cannabinoid Content of Cannabis sativa L.
PLANTS-BASEL
Authors: Burgel, Lisa; Hartung, Jens; Schibano, Daniele; Graeff-Hoenninger, Simone
Abstract
The impact of exogenously applied plant growth regulators (PGR), 1-naphthalenaecetic acid (NAA), 6-benzylaminopurine (BAP), and a mixture of both (NAA/BAP-mix), was investigated in regard to plant height, length of axillary branches, number of internodes, biomass yield and cannabinoid content of three different phytocannabinoid-rich (PCR) Cannabis genotypes. The results showed that total plant height was significantly reduced under the application of NAA (28%), BAP (18%), and NAA/BAP-mix treated plants (15%). Axillary branch length was also significantly reduced by 58% (NAA) and 30% (NAA/BAP-mix). BAP did not significantly reduce the length of axillary branches. The number of internodes was reduced by NAA (19%), BAP (10%), and the NAA/BAP-mix (14%) compared to the untreated control. NAA application influenced the plant architecture of the tested cv. KANADA beneficially, resulting in a more compact growth habitus, while inflorescence yield (23.51 g plant(-1)) remained similar compared to the control (24.31 g plant(-1)). Inflorescence yield of v. 0.2x and cv. FED was reduced due to PGR application while cannabinoid content remained stable. Overall, the application of PGR could be used on a genotype-specific level to beneficially influence plant architecture and optimize inflorescence yield per unit area and thus cannabinoid yield, especially in the presence of space limitations under indoor cultivation.