Injectable calcium phosphate foams for the delivery of Pitavastatin as osteogenic and angiogenic agent

Abstract

Apatitic bone cements have been used as a clinical bone substitutes and drug delivery vehicles for therapeutic agents in orthopedic applications. This has led to their combination with different drugs with known ability to foster bone formation. Recent studies have evaluated Simvastatin for its role in enhanced bone regeneration, but its lipophilicity hampers incorporation and release to and from the bone graft. In this study, injectable calcium phosphate foams (i‐CPF) based on α‐tricalcium phosphate were loaded for the first time with Pitavastatin. The stability of the drug in different conditions relevant to this study, the effect of the drug on the i‐CPFs properties, the release profile, and the in vitro biological performance with regard to mineralization and vascularization were investigated. Pitavastatin did not cause any changes in neither the micro nor the macro structure of the i‐CPFs, which retained their biomimetic features. PITA‐loaded i‐CPFs showed a dose‐dependent drug release, with early stage release kinetics clearly affected by the evolving microstructure due to the setting of cement. in vitro studies showed dose‐dependent enhancement of mineralization and vascularization. Our findings contribute towards the design of controlled release with low drug dosing bone grafts: i‐CPFs loaded with PITA as osteogenic and angiogenic agent.

Controlled Delivery of Curcumin and Vitamin K2 from Hydroxyapatite-Coated Titanium Implant for Enhanced in Vitro Chemoprevention, Osteogenesis, and in Vivo Osseointegration

“…Furthermore, the cumulative release kinetics for both curcumin and vitamin K2 are best fitted with the Korsmeyer–Peppas model, to further analyze the drug release kinetics. The diffusion exponent or n value from the Korsmeyer-Peppas plot for are less than 0.45 for both curcumin and vitamin K2 loaded Ti implants, which corresponds to Fickian diffusion mechanism . Although this model has been previously used to define drug release profiles from polymeric matrix, nowadays various studies have reported its application in porous ceramics drug delivery system.…”

“…The diffusion exponent or n value from the Korsmeyer-Peppas plot for are less than 0.45 for both curcumin and vitamin K2 loaded Ti implants, which corresponds to Fickian diffusion mechanism. 38 Although this model has been previously used to define drug release profiles from polymeric matrix, nowadays various studies have reported its application in porous ceramics drug delivery system. Dissolution of HA coating is an important parameter that not only regulates the durability and stability of the coating but also controls the drug release kinetics.…”

Dual-Drug Delivery via Zein In Situ Forming Implants Augmented with Titanium-Doped Bioactive Glass for Bone Regeneration: Preparation, In Vitro Characterization, and In Vivo Evaluation

“…Pitavastatin enhances the osteoblastic activity by several mechanisms, as mentioned previously. It induces the production of several vascular endothelial growth factors and stimulates BMP-2 and osteocalcin production as mentioned elsewhere [98].…”

Adjuvant Drug-Assisted Bone Healing: Advances and Challenges in Drug Delivery Approaches

“…The foams released pitavastatin ( Figure 3) by an initial burst. In vitro, pitavastatin delivery increased BMP-2 and VEGF expression indicating advantageous osteogenic and angiogenic effects [60]. Furthermore, pravastatin ( Figure 3) can be used in bone regenerative applications as well.…”