Benzoic Acid-loaded Solid Lipid Nanoparticles En-hances Endometrial Receptivity through Upregulation of LIF and Integrin αVβ3

Background: Embryo implantation is the crucial step for a successful pregnancy. Diverse factors, including adhesion mol-ecules, growth factors, and cytokines are important for embryo implantation through improving endometrial receptivity. Ben-zoic acid (BA) is an aromatic carboxylic acid, whose positive effects on endometrial receptivity have been demonstrated, but the poor water solubility and low bioavailability have limited its therapeutic potential. Therefore, employing a nanoparticu-late delivery system may enhance BA bioavailability. The pre-sent study proposed to develop solid lipid nanoparticles (SLNs) as a delivery system for improving BA effects on endometrial receptivity.Materials and Methods: BA-loaded SLNs was prepared by hot homogenization technique and the nanoparticles character-istic include size, encapsulation efficiency and morphological behavior was determined by dynamic light scattering tech-nic, ultrafiltration method and Scanning electron microscopy (SEM), respectively. Cytotoxicity of BA and prepared SLNs on endometrial cell line was evaluated by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Finally endometrial cells were treated with BA and BA-loaded SLNs for 48 h and expression of receptivity related genes evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR).Results: The nanoparticles with appropriate characteristics (particle size of 90 nm and Encapsulation Efficiency of 81%) were prepared. BA-loaded SLNs displayed a good stability for 4 weeks of storage at 4-8°C. No apparent cytotoxicity for SLNs and BA was considered which indicating the biocompatibility of the nanocarriers. Expression experiments revealed that BA and BA-loaded SLN upregulate expression of leukemia inhibi-tory factor (LIF) and Integrin αVβ3. Results also demonstrated that upregulation of LIF and Integrin αVβ3 will intensify when BA is loaded into SLN suggesting capability of SLNs in the more precise delivery of BA into cells than free BA.Conclusion: The results strengthen our hope that loading BA into SLNs could possibly overcome the therapeutic limitations of BA and make it more effective in enhancing endometrial re-ceptivity.

Keywords:

Benzoic Acid , Receptivity , Endometrium , SLN