Follicle Stimulating Hormone Receptor Targeted And Inhibited By Nanoparticular In The Establishment Of Premature Ovarian Failure Model Of Rat

Premature ovarian failure is defined as a primary ovarian defect characterized by absent menarche (primary amenorrhea) or premature depletion of ovarian follicles/arrested folliculogenisis before the age of40years (secondary amenorrhea). POF affects approximately:one in10,000women by age20; one in1,000women by age30; one in100women by age40. The familial form of POF is rare, representing4to31%of all cases of POF. Although the incidence of POF is increasing, we have known little about it’s pathogenesis. For the study of etiopathology and evolution about POF, and the better treatment of it, it’s needed to establish a animal model which is not only ideal and credible but also in accord with the etiology. Targeted therapy has a high degree of selectivity, the side effect of drugs to other unrelated organs can be greatly lowered. For searching of a more effective method to establish a animal model of POF and inhibit the function of FSHR, Our project constructed a target-oriented drug delivery system-follicle stimulating hormone (FSH) peptide modified nanoparticulate system-which was mediated by follicle stimulating hormone receptor (FSHR).In the first part, rFSHβ32-modified nanoparticles was prepared by incorporating malcimide into one end of PEG-PLA copolymer and using its thiol group binding reactivity to conjugate with rFSHβ32-52. The mean size of the well-prepared nanoparticles was100nm(NP) and120nm(rFSHβ32-NP). The zeta potential was about-14mV.After the surface modification with rFSHβ32-52, the size increases in a certain extent, the zeta potential has no significant change.In order to evaluate the capacity of rFSHP32-52for drug delivery into normal granulocyte, in the second part, a lipophilic fluorescent probe,coumarin-6incorporated rFSHβ32-NP was used. It shows that the rFSHβ32has the ability to orientation. By comparing with FSHR negative SKOV3, the uptake amount of both CaOV3and primary granulocyte was significantly higher. It indicates that the rFSHβ32has the active targeting effect. In conclusion, the rFSHβ32-NP drug delivery system constructed in this project, was capable of delivering more drugs into normal granulocytes of rat with a high selectivity mediOur research established a strong experimental foundation for the further study of the establishment of POF’s animal model.