Abstract
The lack of safety, efficacy, and specificity has made the delivery of anti-osteoporotic drugs at a proper dose a challenge. In our study, cathepsin K inhibitor loaded poly (D, L-lactide-co-glycolide) derived lipid hybrid nanoparticles (DNPs) were modified with bone-specific polyaspartic acid [(Asp)8-DNPs] to treat osteoporosis. (Asp)8-DNPs showed its hydroxyapatite binding affinity and achieved a sustained release of cathepsin K inhibitor for up to 5 days. Cathepsin K inhibitor loaded (Asp)8-DNPs significantly decreased the tartrate-resistant acid phosphatase (TRAP) activity and resorption-related genes in osteoclasts. Animal studies also exhibited high accumulation of (Asp)8-DNPs in the tibia and femur and a greater bone mass in trabecular bone and better organized three-dimensional architecture in osteoporotic rat models. Herein, the bone targeting drug delivery system show its potential in treatment of osteoporosis.
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