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Sildenafil citrate–loaded targeted nanostructured lipid carrier enhances receptivity potential of endometrial cells via LIF and VEGF upregulation

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Abstract

The main objective of this research is to prepare sildenafil citrate (SC)–loaded arginyl-glycyl-aspartic acid (RGD)–containing nanostructured lipid carrier (SC-loaded NLC-RGD) and evaluate their effects on the receptivity potential of endometrial cells. Hot homogenization method was used to prepare SC-loaded NLC-RGD. Then, size, drug encapsulation, and morphology of prepared nanoparticles were studied by photon correlation spectroscopy technic, ultrafiltration method, and scanning electron microscopy, respectively. Subsequently, the influence of SC-loaded NLC-RGD on endometrial receptivity was evaluated by in vitro implantation assay. Finally, expression of vascular endothelial growth factor (VEGF), leukemia inhibitory factor (LIF), and integrin beta 3 (as endometrial receptivity markers) was assessed in SC-loaded NLC-RGD-treated endometrial cells by reverse transcription polymerase chain reaction (RT-PCR). Particles with a nano-size diameter (92.7 nm), appropriate polydispersity index (0.21), spherical morphology, and acceptable loading efficiency were prepared. In vitro implantation assay showed that SC, SC-loaded NLC, and SC-loaded NLC-RGD improve the rate of endometrial attachment potential by 1.6 ± 0.4, 1.7 ± 0.3, and 2.3 ± 0.3 times, respectively. Analysis of RT-PCR results showed the enhancing mRNA of LIF and VEGF in SC-treated endometrial cells. Results also confirmed the higher influence of SC-loaded NLC-RGD on gene expression patterns in comparison to SC. Using NLC-RGD as a carrier to deliver SC to endometrial cells is an effective approach to improve endometrial receptivity. Upregulation of LIF and VEGF is the probable mechanism by which SC enhances the endometrial receptivity potential.

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Data availability

Data generated during this study are included in the supplementary material.

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Acknowledgements

The authors would like to thank the Student Research Committee of Tabriz University of medical sciences for their kind assistance and financial support (Grant number: 60989).

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Authors and Affiliations

  1. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran

    Hamed Hajipour

  2. Women’s Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Roshanak Sambrani & Zahra Mirzamohammadi

  3. Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Marjan Ghorbani

  4. Department of Reproductive Biology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

    Mohammad Nouri

Authors
  1. Hamed Hajipour
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  2. Roshanak Sambrani
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  3. Marjan Ghorbani
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  4. Zahra Mirzamohammadi
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  5. Mohammad Nouri
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Contributions

HH and MN conceived and designed research. HH and MG conducted experiments. HH, RS, and ZM analyzed data. HH wrote the manuscript. MG, RS, and ZM revised the manuscript. MN supervised the study. All authors read and approved the manuscript, all data were generated in-house, and no paper mill was used.

Corresponding author

Correspondence to Mohammad Nouri.

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The procedure of the study was approved by the Ethical Committee of Tabriz University of Medical Sciences (IR.TBZMED.VCR.REC.1397.273).

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The authors declare no competing interests.

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Hajipour, H., Sambrani, R., Ghorbani, M. et al. Sildenafil citrate–loaded targeted nanostructured lipid carrier enhances receptivity potential of endometrial cells via LIF and VEGF upregulation. Naunyn-Schmiedeberg's Arch Pharmacol 394, 2323–2331 (2021). https://doi.org/10.1007/s00210-021-02153-8

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  • DOI: https://doi.org/10.1007/s00210-021-02153-8

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