Abstract

Drug delivery systems are a new approach to increase therapeutic efficacy and to reduce the side effects of traditional treatments. Calcium phosphates (CaPs) have been studied as drug delivery systems, especially in bone diseases. However, each system has some particularities that depend on the physical and chemical characteristics of the biomaterials and drug interaction. In this work, granulated CaPs were used as a matrix for loading the anticancer drug carboplatin using the high-vacuum method. Five compositions were applied: hydroxyapatite (HA), β-tricalcium phosphate (β-TCP), biphasic HAp 60%/β-TCP 40% (BCP), β-TCP/MgO nanocomposite, and β-TCP/SiO2 nanocomposite. Carboplatin drug in 50, 60, and 70 mg/g was precipitated on the surface of CaPs. Morphological, chemical and surface modifications in the carboplatin-CaPs were investigated by scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), backscattered electron microscopy (BSE), X-ray diffraction (XRD), X-ray fluorescence spectroscopy (XRF), Fourier transform infrared (FT-IR), and Raman spectroscopy. The characterization of the CaP-carboplatin biomaterials showed heterogeneous crystalline precipitation of the drug, and no morphological modifications of the CaPs biomaterials. The in vitro release profile of carboplatin from CaPs was evaluated by the ultraviolet-visible (UV-Vis) method. The curves showed a burst release of upon 60% of carboplatin loaded followed by a slow-release of the drug for the time of the study. The results were typical of a low-interaction system and physisorption mechanism. The high-vacuum method permitted to load the high amount of carboplatin drug on the surface of the biomaterials despite the low interaction between carboplatin and CaPs.

Highlights

  • MethodsCalcium carbonate (CaCO3) from Synth, batch number 63767, and phosphoric acid H3PO4−85 wt% in water) from Dinamica, batch number 68436, were used in the synthesis of granular biomaterials

  • Calcium phosphate (CaP) biomaterials are used as bone substitutes and as materials in the regeneration tissue process due to their similarities with natural apatites

  • HA and β-tricalcium phosphate (β-TCP) were prepared by the wet chemical method, modified from a previously published study [45], using calcium carbonate (CaCO3) and phosphoric acid (H3PO4) in the quantities required for the formation of precipitates with the desired Ca/P molar ratio

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Summary

Methods

Calcium carbonate (CaCO3) from Synth, batch number 63767, and phosphoric acid H3PO4−85 wt% in water) from Dinamica, batch number 68436, were used in the synthesis of granular biomaterials. HA and β-TCP were prepared by the wet chemical method, modified from a previously published study [45], using calcium carbonate (CaCO3) and phosphoric acid (H3PO4) in the quantities required for the formation of precipitates with the desired Ca/P molar ratio. Powders of hydrated calcium phosphate precipitated in the synthesis were sieved on a 100 μm mesh. They were calcined at 900 ̊C for 2 hours, and the obtained nanostructured powder of HA and β-TCP were used to produce granulate biomaterials. The material was dried in a rotatory evaporator, and the granular biomaterials recovered were sieved and sintered at 1,100 ̊C for 2 hours

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