Optimizing locally delivered periodontitis therapy: Development of chitosan‐hydroxyapatite‐encapsulated drug via electrospraying

Abstract This study presents the development of an optimized drug delivery system for periodontitis treatment utilizing chitosan‐hydroxyapatite nanoparticles. Employing the electrospraying technique, researchers encapsulated the antibiotic amoxicillin within chitosan‐hydroxyapatite composite matrices while varying the concentrations of chitosan and hydroxyapatite nanoparticles. The resulting microparticles displayed sizes ranging from 276 to 386 μm. Characterization of the produced drug encapsulations indicated that higher concentrations of chitosan and hydroxyapatite resulted in the formation of larger particles with rougher surfaces, increased mechanical strength, and enhanced thermal stability. Notably, nanoindentation analysis revealed an increase in hardness from 0.21 to 0.35 GPa, and in elastic modulus from 5.32 to 8.72 GPa with escalating chitosan and hydroxyapatite content, meeting or surpassing requirements for load‐bearing regenerative biomaterials. In vitro drug release assessments exhibited sustained amoxicillin release over 24 h, predominantly through diffusion and dissolution mechanisms. Formulations with lower polymer and mineral content showcased elevated release rates, with the F1 encapsulation (0.5% chitosan, 0.2% HAP) achieving a cumulative release of 78.3 ± 3.2% in contrast to 65.1 ± 2.7% for the F5 formulation (2.5% chitosan, 1% HAP). These encapsulations selectively modulated the overproduction of proinflammatory cytokines, including IL‐1β, IL‐6, and TNF‐α, in gingival fibroblasts and osteoblasts without compromising cell viability. An artificial neural network (ANN) model accurately forecasted the material properties and biological performance of the formulations based on their compositional variations, yielding correlation coefficients exceeding 0.97. This computational platform offers a virtual screening tool for refining regenerative and drug delivery therapies. The developed chitosan‐hydroxyapatite microparticulate system demonstrates promising potential for prolonged treatment of periodontitis through controlled antibiotic delivery, improved mechanical properties, and targeted regulation of the inflammatory response.