Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Deemed University, Elite Status and Centre of Excellence (Maharashtra), Mumbai, Maharashtra, India.
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Deemed University, Elite Status and Centre of Excellence (Maharashtra), Mumbai, Maharashtra, India.
Nanomedicine. 2020 Feb;24:102153. doi: 10.1016/j.nano.2020.102153. Epub 2020 Jan 25.
We present salmon calcitonin (SCT) loaded Hydroxyapatite nanoparticles (HAP-NPs) for sublingual osteoporosis therapy. Surface stabilized HAP-NPs were prepared by aqueous precipitation. SCT was loaded by ionic complexation, as confirmed by FTIR. SCT-HAP-NPs exhibited high loading efficiency (85%), average size (100 nm), and zeta potential (~ -25 mv). Stability of SCT was established by circular dichroism spectroscopy and HPLC analysis. Confocal laser scanning microscopy confirmed deep penetration of SCT-HAP-NPs into the mucosa with >4-fold enhancement in permeability relative to SCT solution. Sublingual SCT-HAP-NPs revealed relative bioavailability of ~15% compared to the subcutaneous injection in rabbits (200 IU). Significant and comparable improvement in serum biomarkers with increase in bone mass and mechanical strength and decreased bone erosion compared to subcutaneous SCT was confirmed in ovariectomized (OVX) osteoporosis rat model. Such comparable pharmacodynamic effect at the same dose suggested targeted bone delivery and promise of sublingual SCT-HAP-NPs as a non-invasive alternative to the injection.
我们提出了鲑鱼降钙素（SCT）负载的羟磷灰石纳米颗粒（HAP-NPs）用于舌下骨质疏松症治疗。通过水相沉淀法制备表面稳定的 HAP-NPs。通过离子络合作用负载 SCT，FTIR 证实了这一点。SCT-HAP-NPs 表现出高载药效率（85%）、平均粒径（100nm）和 Zeta 电位（~-25mV）。通过圆二色光谱和 HPLC 分析确定了 SCT 的稳定性。共聚焦激光扫描显微镜证实 SCT-HAP-NPs 能够深入穿透黏膜，与 SCT 溶液相比，渗透性提高了 4 倍以上。与皮下注射相比，在兔（200IU）中，舌下 SCT-HAP-NPs 的相对生物利用度约为 15%。在去卵巢（OVX）骨质疏松症大鼠模型中，与皮下 SCT 相比，SCT-HAP-NPs 可显著改善血清生物标志物，增加骨量和机械强度，减少骨侵蚀。这种相同剂量下的类似药效作用提示了靶向骨递药的可能性，并有望成为注射的非侵入性替代方案。
