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.

中文翻译：

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鲑鱼降钙素羟基磷灰石纳米颗粒的骨靶向递送，用于舌下骨质疏松症治疗（SLOT）。

我们介绍鲑鱼降钙素（SCT）负载羟基磷灰石纳米颗粒（HAP-NPs）用于舌下骨质疏松症的治疗。通过水沉淀制备表面稳定的HAP-NP。FTIR证实，SCT是通过离子络合加载的。SCT-HAP-NPs表现出较高的加载效率（〜85％），平均大小（〜100 nm）和ζ电位（〜-25 mv）。通过圆二色光谱和HPLC分析确定SCT的稳定性。共聚焦激光扫描显微镜证实，相对于SCT溶液，SCT-HAP-NPs深层渗透到粘膜中，渗透率提高了4倍以上。与兔皮下注射（200 IU）相比，舌下SCT-HAP-NPs的相对生物利用度约为15％。在卵巢切除（OVX）骨质疏松大鼠模型中，与皮下SCT相比，血清生物标志物的显着且可比的改善与骨量和机械强度的增加以及骨侵蚀的减少有关。在相同剂量下，这种可比的药效学作用表明靶向骨递送和舌下SCT-HAP-NPs有望作为注射剂的非侵入性替代方法。