Water state effect on drug release from an antibiotic loaded polyurethane matrix containing albumin nanoparticles

Water mobility plays a crucial role in determining transport properties of small molecules in polymer matrices. In particular, in drug delivery systems, water state affects the pharmacokinetics, especially drug absorption, diffusion and release. In the present study, the state of water in an antibiotic-loaded composite consisting of albumin nanoparticles (BSAnp) dispersed into a carboxylated polyurethane (PEUA) has been investigated and compared with that of the single drug-loaded components. The antibiotic cefamandole nafate was used as a model drug. DSC analysis, used to evaluate the freezing and non-freezing water fractions in the hydrated samples, showed that in BSAnp water can adsorb both in the inter-particles regions and inside the particles. With increasing of total adsorbed water amount, the contribution of the freezing water fraction was higher than the non-freezing one. As for PEUA, the majority of water molecules absorbed is in a mobile freezing state (about 60% of the Wtot).As for the PEUA/BSAnp composite, the higher polyurethane phase segregation induced by the nanoparticles as well as the higher non-freezing water fraction significantly enhanced drug uptake with respect to PEUA. Moreover, the greater non-freezing water fraction allowed the drug to penetrate within BSA nanoparticles and to give rise then to a controlled drug release. Indeed, the diffusion barrier exerted by nanoparticles and the matrix prolonged the antimicrobial activity from 4 to 9 days.Finally, the higher polyurethane phase segregation also improved composite mechanical properties, as evidenced in stress–strain experiments and dynamic mechanical analysis.

The water state in an antibiotic-loaded composite drug delivery system consisting of albumin nanoparticles dispersed into a carboxylated polyurethane has been investigated. The non freezing water fraction was accountable for a slower drug release along with the nanoparticle/polyurethane interactions. This latter also improved the system mechanical properties.Figure optionsDownload as PowerPoint slide