The correlation between unexplained infertility and exosomes.

OBJECTIVES: Endometrial receptivity plays the most important role for successful implantation. Increasing endometrial receptivity may improve infertility and increase Assisted Reproductive Technologies success. The aim of this study was to investigate the effect of exosome specific markers CD63 and CD9 which are promising molecules in the pathogenesis and treatment of many diseases on endometrial receptivity in women with unexplained infertility. MATERIAL AND METHODS: This prospective study was conducted between November 2015 and March 2017. Proliferation and secretion periods of endometrial samples from fertile and infertile cases were collected. The paraffin-embedded tissue sections were stained with hematoxylin-eosin for the immunohistochemical analysis distributions of CD63 and CD9. RESULTS: The results of this study demonstrated that the CD63 immunoreactivity was higher in both luminal and glandular epithelium of infertile patients when compared with fertile patients during the proliferative phase (p = 0.009, p = 0.008). In the infertile proliferation phase, endometrium CD9 immunoreactivity was rarely detected in both the luminal and glandular epithelium. In the secretion phase of endometrium, CD9 immunoreactivity was mild in fertile patients, the increased immunoreactivity of CD9 was observed in both luminal and glandular epithelium of infertile patients (p = 0.037, p = 0.037). CONCLUSIONS: Increased levels of CD63 in infertile proliferation phase endometrium should represent an unfavorable signaling. Moreover, the increased levels of CD9 in infertile secretion phase endometrium could be used as a biomarker to evaluate endometrial receptivity. These exosome-specific markers can be considered as potential molecular markers of infertility.

Intranasal and intravenous administration of octa-arginine modified poly(lactic-co-glycolic acid) nanoparticles facilitates central nervous system delivery of loperamide.

OBJECTIVES: The potential of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) surface modified with octa-arginine (R8) for central nervous system (CNS) delivery was investigated. METHODS: PLGA NPs containing coumarin-6 or loperamide were surface modified using R8 and characterised for size, zeta potential, drug loading and release. We examined the cellular uptake of NPs in Madin-Darby Canine Kidney (MDCK) cells and CNS delivery of loperamide in a mouse model following intranasal (i.n.) and intravenous (i.v.) administration. KEY FINDINGS: NPs were 300-350 nm in diameter and of negative zeta potential which neutralised on R8 conjugation. Cellular uptake of R8-PLGA NPs was rapid compared with PLGA NPs and correlated with a high antinociceptive effect in mice by both the i.n. and i.v. routes. Little antinociceptive effect for PLGA NPs was observed reflecting their slow uptake in the in-vitro cell model. CONCLUSION: This study demonstrates the potential of R8-PLGA NPs as carriers of therapeutic agents to the CNS.