Remote-controllable bone-targeted delivery of estradiol for the treatment of ovariectomy-induced osteoporosis in rats
Yuanyuan Guo, Yongwei Liu, Chen Shi, Tingting Wu, Yongzhi Cui, Siyuan Wang, Ping Liu, Xiaobo Feng, Yu He, Dehao Fu
Abstract
Abstract Background Osteoporosis (OP) is a systemic skeletal disease marked by bone mass reduction and bone tissue destruction. Hormone replacement therapy is an effective treatment for post-menopausal OP, but estrogen has poor tissue selectivity and severe side effects. Results In this study, we constructed a poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs)-based drug delivery system to co-load 17β estradiol (E 2 ) and iron oxide (Fe 3 O 4 ) together, modified with alendronate (AL) to achieve bone targeting and realize a magnetically remote-controllable drug release. The NPs were fabricated through the emulsion solvent diffusion method. The particle size was approximately 200 nm while the encapsulation efficiency of E 2 was 58.34 ± 9.21%. The NPs were found to be spherical with a homogenous distribution of particle size. The NPs showed good stability, good biocompatibility, high encapsulation ability of E 2 and excellent magnetic properties. The NPs could be effectively taken up by Raw 264.7 cells and were effective in enriching drugs in bone tissue. The co-loaded NPs exposed to an external magnetic field ameliorated OVX-induced bone loss through increased BV/TV, decreased Tb.N and Tb.Sp, improved bone strength, increased PINP and OC, and downregulated CTX and TRAP-5b. The haematological index and histopathological analyses displayed the NPs had less side effects on non-skeletal tissues. Conclusions This study presented a remote-controlled release system based on bone-targeted multifunctional NPs and a new potential approach to bone-targeted therapy of OP. Graphic abstract