Chitosan (CS) is a linear copolymer of β-(1-4)linked 2-acetamido-2-deoxy-beta-D-glucopyranose and 2-amino-2-deoxy-3-D-glucopyranose, obtained by deacetylation of its parent polymer chitin, the second most abundant in nature after cellulose [1] . The bactericidal action of CS is well known and is due to an electrostatic interaction between NH 3 + groups of CS and phosphoryl groups of phospholipid components and lipopolysaccharides of bacterial cell membranes. This leads to an increase in the permeability formation of pores and finally disrupts the bacterial cell wall [2][3][4] . Bacterial infectious diseases ranging from cutaneous infection to deep-seated life-threatening infections such as pneumonia, endocarditis, septicaemia, osteomyelitis, and other metastatic complications [5][6][7] . Antibiotic are the usual treatment for bacterial infection [8] . Bacterial infectious disease is still responsible for considerable global mortality despite antibiotic treatment [9][10][11] . The major challenges faced by localized treatment of respiratory tract infections are the rapid absorption and clearance of antibiotics from the lungs. A critical obstacle and challenge for bacterial infectious therapy concerns the limited availability of effective biocompatible delivery system for most hydrophobic therapeutic and antimicrobial resistance. Intracellular infections and acquired resistance of infectious microbes are also key challenges [12] .The clinical treatment failure of bacterial infectious disease is associated with low bioavailability of antibiotics, side effects of antibiotics, tissue and cellular barriers, biofilm-related infection and the emergence of resistant bacteria. Polymeric nanoparticles (NPs) and microparticles have been shown to have the potential to provide controlled drug delivery to the lungs, with sustained release of drugs so as to prolong drug

Background:: Chitosan nanoparticles have been extensively studied and used due to their well-recognized applicability in various fields. Chitosan, a natural polysaccharide polymer and is extensively used in pharmaceuticals to deliver a wide variety of therapeutic agents. Chitosan is a biocompatible and biodegradable mucoadhesive polymer that has been extensively used in the preparation of multi particles, particularly nano- and microparticles. Objective:: The main aim of the present study was to optimize the conditions for the preparation of chitosan nanoparticles to get optimal particle size, with optimal zeta potential and narrow polydispersity index, and antibacterial activity. Methods:: Methods include the ionic gelation technique for chitosan nanoparticle preparation. The influence of formulation parameters and process parameters on the Chitosan nanoparticles were investigated. Besides, the suspension stability of the prepared nanoparticles is also assessed on storage at 4°C. Results: clearly showed that the formulation and process parameters showed a significant effect on the physicochemical and morphological characteristics of the chitosan nanoparticles. The chitosan nanoparticles prepared under optimum conditions (chitosan concentration of 0.5% w/v, CS: TPP mass ratio of 1:3, initial pH of chitosan solution of 4.5, stirred at 750 rpm for 30 min) had shown a mean particle size of ~326.8±15 nm, the zeta potential of +28.2 ± 0.5 mV, PDI of 0.21 ± 0.02. The encapsulation of the clarithromycin slightly increased the polydispersity index but the zeta potential of the unloaded nanoparticles was not affected while the particle size increased. Under optimum conditions, clarithromycin encapsulation efficiency into nanoparticles was found to be 70%. Additionally, chitosan-tripolyphosphate nanoparticles were shown to be stable for a minimum of fifteen days in deionized water at 4°C. Conclusion:: The current study concludes on the optimal conditions to formulate the chitosan nanoparticles with optimal physicochemical characteristics.