Formulation and Characterization of Doxorubicin Loaded N‐acetyl Neuraminic Acid Coupled Biodegradable Nanoparticles for Lung Cancer Treatment: In Vitro and In Vivo Assessment

The current research focused on the preparation and evaluation of N‐acetyl neuraminic acid (NANA) coupled chitosan nanoparticles (CHN‐NPs) loaded with Doxorubicin (Dox). The research findings demonstrated positively charged, uniform spherical chitosan particles within the dimension of <200nm, showing suitability for parenteral delivery. Further, Fourier‐transform infrared spectroscopy (FTIR) and X‐ray diffraction (XRD) findings showed good physicochemical compatibility between doxorubicin, polymer and entrapment of the drug within the chitosan nanoparticle matrix. The elemental analysis by X‐ray photoelectron spectroscopy (XPS) analysis confirmed successful conjugation of NANA on chitosan. The release of doxorubicin from prepared nanoparticles showed a pH‐dependent biphasic pattern. The in vitro cell‐line investigation showed that targeted NANA‐modified Dox‐containing CHN‐NPs had more cellular uptake as well as cytotoxicity on A‐549 cell lines in comparison to non‐targeted Dox‐loaded CHN‐NPs and free Dox. The pharmacokinetics and in vivo fluorescent imaging results confirmed that NANA‐modified Dox‐CHN‐NPs showed improved bioavailability and significantly higher targeting ability in the lung region. The serum biochemical and histopathological analysis showed that the NANA‐modified Dox‐loaded CHN‐NPs had minimal off‐target effects, with reduced toxicity. Finally, an in vivo therapeutic study on benzo[a] pyrene induced lung cancer prototype in Swiss albino‐mice showed that NANA‐modified Dox‐loaded CHN‐NPs effectively treated the lung cancer. This study introduces a promising drug delivery system designed to specifically target lung cancer.