The effect of porosity on drug release kinetics from vancomycin microsphere/calcium phosphate cement composites

Abstract

The influence of porosity on release profiles of antibiotics from calcium phosphate composites was investigated to optimize the duration of treatment. We hypothesized, that by the encapsulation of vancomycin-HCl into biodegradable microspheres prior admixing to calcium phosphate bone cement, the influence of porosity of the cement matrix on vancomycin release could be reduced. Encapsulation of vancomycin into a biodegradable poly(lactic co-glycolic acid) copolymer (PLGA) was performed by spray drying; drug-loaded microparticles were added to calcium phosphate cement (CPC) at different powder to liquid ratios (P/L), resulting in different porosities of the cement composites. The effect of differences in P/L ratio on drug release kinetics was compared for both the direct addition of vancomycin-HCl to the cement liquid and for cement composites modified with vancomycin-HCl-loaded microspheres. Scanning electron microscopy (SEM) was used to visualize surface and cross section morphology of the different composites. Brunauer, Emmett, and Teller-plots (BET) was used to determine the specific surface area and pore size distribution of these matrices. It could be clearly shown, that variations in P/L ratio influenced both the porosity of cement and vancomycin release profiles. Antibiotic activity during release study was successfully measured using an agar diffusion assay. However, vancomycin-HCl encapsulation into PLGA polymer microspheres decreased porosity influence of cement on drug release while maintaining antibiotic activity of the embedded substance.

3D printed TCP-based scaffold incorporating VEGF-loaded PLGA microspheres for craniofacial tissue engineering

“…Pore size, interconnectivity and geometry of scaffolds can also influence drug loading and control over release rate in vivo [78]. In addition, biodegradability of the drug carrier plays a crucial role in drug release.…”

Drug delivery from injectable calcium phosphate foams by tailoring the macroporosity–drug interaction

“…Although some approaches successfully prevented the risk of antibiotic resistance by releasing almost all the drug loaded [39], the dosage forms did not present an adequate macrostructure to enhance bone ingrowth. The calcium phosphate foams presented in this study exhibit a progressive release profile up to 1 mg in 5 days, corresponding to 55% of the quantity loaded in 2D-CPC, with potential for complete release and a simultaneous interconnected macroporosity of around 25 % (Fig.…”

Multiple characterization study on porosity and pore structure of calcium phosphate cements

“…Different models can be applied to convert the data in pore size distribution, one of the most common being the BarrettJoyner-Halenda (BJH) method [16], which makes use of the combined effect of capillary condensation in the inner pore volume, and physical adsorption on the pore ¨ w alls, and assumes that pores are cylindrical. It provides the pore size distribution at the nanometer range [20].…”

“…In the field of CPCs, however, it has generally been limited to the characterization of the specific surface area [1,[16][17][18], using the Brunauer-Emmet-Teller (BET) theory [19], which involves a model for the adsorption £ of a monolayer of gas onto the surface of a material. However, capillary condensation measurements allow also to correlate vapour pressure and pore dimensions, providing information on pore size distribution in the material.…”