Title:Molecular Complex of HSIM-loaded Polymeric Nanoparticles: Potential
Carriers in Osteoporosis
Volume: 24
Issue: 13
关键词:
羟基磷灰石，辛伐他汀，靶向，纳米颗粒，聚乳酸-羟基乙酸，缓释。
摘要:
Background: Statins, especially simvastatin promote bone formation by stimulating the
activity of osteoblasts and suppressing osteoclast activity via the BMP-Smad signaling pathway.
Statins present the liver first-pass metabolism. This study attempts to fabricate and evaluate simvastatin
functionalized hydroxyapatite encapsulated in poly(lactic-co-glycolic) acid (PLGA) nanoparticles
(HSIM-PLGA NPs) administered subcutaneously with sustained release properties for effective
management of osteoporosis.
Methods: Simvastatin functionalized hydroxyapatite (HSIM) was prepared by stirring and validated
by docking studies, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy
(SEM), and X-ray diffraction (XRD). Further, HSIM-loaded PLGA nanoparticles (HSIM-PLGA
NPs) were developed via the solvent emulsification method. The nanoparticles were evaluated
for zeta potential, particle size, entrapment efficiency, stability studies, and in vitro drug release
studies. in vitro binding affinity of nanoparticles for hydroxyapatite was also measured. Bone morphology
and its effect on bone mineral density were examined by using a glucocorticoid-induced
osteoporosis rat model.
Results: The optimized nanoparticles were found to be amorphous and showed no drug-polymer interaction.
The particle size of formulated nanoparticles varied from 196.8 ± 2.27nm to 524.8 ± 5.49
nm and the entrapment efficiency of nanoparticles varied from 41.9 ± 3.44% to 70.8 ± 4.46%, respectively.
The nanoparticles showed sustained release behaviour (75% in 24 hr) of the drug followed
by non-fickian drug release. The nanoparticles exhibited high binding affinity to bone cell receptors,
increasing bone mineral density. A significant difference in calcium and phosphorous levels
was observed in disease and treatment rats. Porous bone and significant improvement in porosity
were observed in osteoporotic rats and treated rats, respectively (P < 0.05).
Conclusion: Bone-targeting nanoparticles incorporating functionalized simvastatin can target
bone. Thus, in order to distribute simvastatin subcutaneously for the treatment of osteoporosis, the
developed nanoparticles may act as a promising approach.
