pH-Dependent Diffusion-Dissolution Transition in Vancomycin-Loaded Calcium Phosphate-Liposome Nanoparticles

Abstract

Drug delivery systems (DDSs) have attracted significant attention due to their ability to enhance therapeutic efficacy while minimizing side effects. In this study, vancomycin (VCM)-loaded calcium phosphate-liposome (CaPLip) composite nanoparticles were developed as a pH-responsive drug delivery system. The CaPLip nanoparticles were fabricated by in situ calcium phosphate precipitation on preformed liposomal templates in the presence of VCM, allowing the drug to be incorporated within the calcium phosphate matrix and adsorbed onto the CaP-coated surface (VCM-CaPLip). Structural and morphological characterization using FT-IR, XRD, and TEM confirmed the successful formation of calcium phosphate-coated liposomal nanoparticles with particle sizes ranging from 300 to 700 nm and a negative surface charge. The developed system exhibited an overall drug-loading efficiency of 47.28% and effectively reduced the initial burst release under physiological conditions. Equilibrium adsorption studies performed using preformed CaPLip nanoparticles demonstrated that VCM adsorption was well described by the Langmuir isotherm, indicating a high affinity of VCM for the CaP-coated surface under equilibrium conditions. Drug release studies at pH 4.0, 6.5, and 7.4 revealed pronounced pH-dependent behavior, with sustained release at pH 7.4 and accelerated release under acidic conditions. Changes in electrical conductivity provided supporting evidence for calcium phosphate dissolution accompanying drug release under acidic conditions. Kinetic analysis indicated a transition from predominantly diffusion-controlled release at physiological pH to diffusion-dissolution coupled release under acidic conditions. These findings demonstrate that CaPLip nanoparticles provide an effective pH-responsive antibiotic delivery platform and show potential for controlled drug release in infection-associated mildly acidic microenvironments.