TTCP-DCPA Based Calcium Phosphate Cements Containing Hybrid Microparticles as Drug Carriers

Abstract

In recent years, considerable attention has been focused on the development of new composite materials for application as drug delivery systems. In this field, calcium phosphate cements (CPCs) are often employed as support to delivery of drugs, but their behavior has some drawback related to the so-called burst effect. The aim of this work was to develop new CPCs formulations from synthesized tetracalcium phosphate (TTCP), dicalcium phosphate anhydrous TTCP and drug-containing hybrid microparticles (DCHM). The main function of these DCHM is providing nuclei of high concentration of drugs into the CPCs. The DCHM were synthesized via the sol-gel method from a bridged precursor of the type (H3CO)3 – Bridge – (OCH3)3 and aspirin (AS) as model drug. The inorganic polycondensation reached 89.5 % as calculated by 29Si NMR. The analysis by small angle X-ray scattering (SAXS) reveled a short range structural ordering in the DCHM at molecular level. Effective incorporation of AS inside the microspheres was detected by FTIR spectroscopy. In vitro tests of DCHM according to ISO 10993-5 revealed non-cytotoxic behavior. Four CPCs formulations containing 0, 1, 5 and 10 wt % of DCHM, were evaluated. The presence of DCHM did not modify neither the degree of conversion to low-crystallinity HA nor the measured setting times of the CPCs, however, the amount of incorporated microparticles considerably affected the degree of porosity (macropores of 200 µm) and interconnectivity of the cement matrix.