Bone targeted delivery of salmon calcitonin hydroxyapatite nanoparticles for sublingual osteoporosis therapy (SLOT)

• Published in: Nanomedicine 2020-02, Vol.24, p.102153-102153, Article 102153
• Main Authors: Kotak, Darsheen J., Devarajan, Padma V.
• Format: Article
• Language: English
• Subjects: Bone targeting; Hydroxyapatite nanoparticles; Osteoporosis; Ovariectomy; Salmon calcitonin; Sublingual delivery
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2020.102153

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. Sublingual SCT-HAP-NPs revealed deep and enhanced sublingual permeation with good bio-enhancement. Improved mechanical strength and bone mass density, with decrease in number of resorption pits suggested bone targeting and improved efficacy of SCT-HAP-NPs. [Display omitted]