Development of chitosan-functionalized PLGA/alginate polymeric nanoparticles for controlled doxycycline release in pediatric Streptococcus pneumoniae infections.

Streptococcus pneumoniae continues to be a leading pathogen responsible for severe respiratory related diseases among children, often demanding prolonged treatment with antibiotics. In this study, we developed a chitosan-modified PLGA/alginate nanoparticles for controlled doxycycline delivery (CS-PLGA/Alginate@Doxy NPs) with the goal of improving therapeutic effect while reducing dosing frequency and treatment-related difficulties. The fabricated NPs demonstrated a well-defined spherical structure with an average diameter close to 50-70 nm, a stable negative surface charge, and a notably high drug encapsulation capability, confirming their suitability for inhalation-based antimicrobial therapy. In vitro drug release studies confirmed sustained Doxy release over 72 h under different pH conditions. Antibacterial activity was evaluated against of S. pneumoniae, showing significantly improved bactericidal activity compared to free Doxy and other combinations. Further, the crystal violet assay and fluorescent microscopy analysis reveals that, the S. pneumoniae biofilm thickness was significantly reduced with visible disintegration of EPS matrix when exposed to CS-PLGA/Alginate@Doxy NPs. Cytocompatibility assays on fibroblast (L929) and human lung epithelial cells (L-132) confirmed the safety profile of the CS-PLGA/Alginate@Doxy NPs for pediatric use. The results proposed that the fabricated CS-PLGA/Alginate@Doxy NPs signifies a promising targeted delivery platform for the effective management of pediatric pneumococcal infections.