An Experimental Study On Drug-loaded System Based On Bone-targeted Multi-Function PLGA Nanoparticles Mediating Estradiol To Treat Postmenopausal Osteoporosis

Background Hormone replacement therapy is an effective treatment for postmenopausal osteoporosis,but estrogen has poor tissue selectivity and severe side effects.If estrogen could be imported targeting to bone tissue,it will be bound to reduce the toxic effects to non-bone tissues or organs.Objective This study was to build a drug-loaded system based on bone-targeted multi-function nanoparticles,in order to mediate estrogen to treat postmenopausal osteoporosis.Methods The drug carrier of nanoparticles was poly(lactic-co-glycolic acid),which was modified with alendronate and polyethylene glycol,and encapsulated with estradiol.Diameter,polymer dispersity index,Zeta potential,encapsulation efficiency and stability of nanoparticles were analysed.Then nanoparticles were labeled with fluorescent dyes,and the distribution of nanoparticles in rats was observed after an tail vein injection,in order to confirm the bone targeting ability.The rat model was constructed by ovariectomy method,and the therapeutic effect of nanoparticles was evaluated after intravenous administration.Results Nanoparticles were prepared by emulsion solvent diffusion method.The particle size was approximately 200 nm while the encapsulation efficiency was 58.3±9.2.The results of electron microscopy showed that the nanoparticles were spherical and the distribution of particle size was homogeneous.Stability experiment confirmed that the nanoparticles were stable.Fluorescently-labeled nanoparticles confirmed that the nanoparticles had a certain degree of bone targeting ability and circulation time was increased after modification of alendronate and polyethylene glycol.The results of intravenous administration showed that the rat model of osteoporosis was successfully constructed,and the optimal therapeutic effect was achieved with multi-function nanoparticles.Conclusion Based on the carrier of poly(lactic-co-glycolic acid),which was modified with alendronate and polyethylene glycol,and encapsulated with estradiol,a drug-loaded system based on bone-targeted multi-function nanoparticles was successfully built,thus providing a new idea for bone-targeted therapy of osteoporosis.