Synthesis and functionalization of zinc phosphate@polyglycidyl methacrylate composites for antimicrobial drug immobilization and controlled release: an in vitro study

Abstract

Nowadays, the development of functional polymer-coated inorganic composite particles is an important topic of investigation for biomedical applications. Although several studies have tried to design hybrid nanocomposites, this study aimed to synthesize functionalized and colloidally stable ZnP composites for bio-related applications. Herein, a facile three-step method was used to synthesize carboxyl and amine functionalized polyglycidyl methacrylate (PGMA) coated zinc phosphate (ZnP@PGMA) particles. First, ZnP particles were synthesized using an aqueous precipitation method. Then, the synthesized ZnP particles were coated with PGMA via aqueous seeded free-radical polymerization of GMA. PGMA-coating significantly reduced the aggregation tendency of ZnP nanoparticles in aqueous medium. Finally, the surface of ZnP@PGMA particles was further functionalized with L-cysteine (Cys) and diethylenetriamine (DETA) to increase the hydrophilicity and surface functionality of the composite particles. Fourier transform infrared, energy dispersive X-ray, and X-ray photoelectron spectroscopic analyses confirmed the formation and functionalization of ZnP@PGMA particles. An X-ray diffraction study revealed the tetrahedral hopeite structure of ZnP particles, and their further functionalization did not alter the initial crystal lattice structure. Scanning electron and transmission electron micrographs showed that the ZnP particles were indeed spherical nanoparticles although the polymerization and functionalization processes significantly altered their morphologies. Thermogravimetric analysis revealed the thermal degradation of the polymeric matrix as well as the stability of ZnP particles and their functionalized composites. An in vitro trypsin adsorption study indicated a minimal amount of adsorption on the carboxy-amine surface-modified composites compared with that on unfunctionalized ZnP@PGMA particles. Next, the antibacterial drug, ceftriaxone sodium (CFX), was physically immobilized onto the surface of carboxyl and amine functionalized composite particles. An in vitro drug release study showcased sustained release kinetics of the loaded-CFX molecules. Finally, in vitro antibacterial assay of the CFX-loaded composite particles against two different bacterial strains, namely Bacillus cereus and Pseudomonas aeruginosa, showed significant inhibition of bacterial growth in agar media. Hence, carboxyl and amine functionalized ZnP@PGMA composite particles can be used as an effective drug-delivery agent against multi-drug-resistant bacterial infections.