The aim of this study was to develop a ciclopirox (CXP) topical nano spray using nanotechnology to enhance drug bioavailability and skin absorption. A precipitation method was employed to incorporate CXP in its nano particulate form, using chitosan as the polymer. Chitosan nanoparticles (CT NPs) possess unique properties that make them highly suitable for biological applications. The study focused on investigating the penetration behavior of chitosan nanoparticles (nano spray) through artificial skin, with the goal of developing them as effective skin delivery systems for medications. The nanoparticles had an average size of 640 nm, with a positive or negative surface potential and a polydispersity index (PDI) of 0.298. A thorough analysis of the nano spray was conducted using several scientific techniques, including X-ray diffractometry, scanning electron microscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry (DSC), as well as in vitro release and diffusion studies. Additionally, cell viability was evaluated using the MTT assay, and blood compatibility was tested through a hemolysis test. The study also assessed the levels of the anti-inflammatory cytokine IL-2 in the lungs of mice using RNA extraction, reverse transcription, and polymerase chain reaction (RT-PCR). The drug dissolution and diffusion rates showed a significant improvement compared to the pure reference sample. Therefore, the CXP nano spray appears to be an efficient and practical method to enhance skin penetration, bioavailability, and permeability. Based on the results, the CXP nano spray holds potential as a promising treatment for fungal infections, particularly for skin diseases.