Osteogenic and Anti-Inflammatory Behavior of Injectable Calcium Phosphate Loaded with Therapeutic Drugs

Abstract

Bone fractures related to musculoskeletal disorders determine long-term disability in older people with a consequent significant economic burden. The recovery of pathologically impaired tissue architecture allows avoiding bone loss-derived consequences such as bone height reduction, deterioration of bone structure, inflamed bone pain, and high mortality for thighbone fractures. Actually, standard therapy for osteoporosis treatment is based on the systemic administration of biphosphonates and anti-inflammatory drugs, which entail several side effects including gastrointestinal (GI) diseases, fever, and articular pain. Hence, the demand of innovative therapeutic approaches for locally treating bone lesions has been increasing in the last few years. In this scenario, the development of injectable materials loaded with therapeutically active agents (i.e., anti-inflammatory drugs, antibiotics, and peptides mimicking growth factors) could be an effective tool to treat bone loss and inflammation related to musculoskeletal diseases, including osteoporosis and osteoarthritis. According to this challenge, here, we propose three different compositions of injectable calcium phosphates (CaP) as new carrier materials of therapeutic compounds such as bisphosphonates (i.e., alendronate), anti-inflammatory drugs (i.e., diclofenac sodium), and natural molecules (i.e., harpagoside) for the local bone disease treatment. Biological quantitative analyses were performed for screening osteoinductive and anti-inflammatory properties of injectable drug-loaded systems. Meanwhile, cell morphological features were analyzed through scanning electron microscopy and confocal investigations. The results exhibited that the three systems exerted an osteoinductive effect during later phases of osteogenesis. Simultaneously, all compositions showed an anti-inflammatory activity on inflammation in vitro models.

Biomimetic Citrate-Coated Luminescent Apatite Nanoplatforms for Diclofenac Delivery in Inflammatory Environments

“…Nanocarriers of different composition have also been studied for the delivery of DF for biomedical applications, such as polysaccharides [ 63 ], poly(ε-caprolactone) micelles [ 64 , 65 ], magnetic NPs [ 66 ]. Concerning the adsorption of DF on any form of apatite as adsorbent, it was recently reported the adsorption on amino hydroxyapatite/chitosan/glutaraldehyde hybrids composites at pH 6 [ 67 ], and the release of DF from injectable CaP-loaded systems to treat inflammation [ 68 ], but these authors did not study the adsorption isotherms, nor used luminescent apatites, therefore we cannot compare our results. In line with what we reported here (see beyond), in all these cases the compositions showed an anti-inflammatory activity on inflammation in vitro and in vivo experimental models.…”

Sudoku of porous, injectable calcium phosphate cements – Path to osteoinductivity

“…With the incorporation of drugs multi-target therapy is possible – incorporated drugs can be able to not only treat inflammation, but also inhibit bone degeneration [ 192 ]. Farbod et al showed that sustained release drugs can also be engineered.…”

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