Development and Characterization of Chitosan Nanoparticles for Inhalable Antibiotics Delivery

Abstract

The rising prevalence of multidrug-resistant (MDR) pathogens, particularly Acinetobacter baumannii, has significantly complicated the treatment of hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). This calls for the development of novel treatment strategies and alternative drug delivery approaches. This thesis explores the development and characterization of inhalable chitosan-based nanoparticles as a pulmonary drug delivery platform for targeting MDR respiratory infections. Chitosan nanoparticles were synthesized via the ionic gelation method using tripolyphosphate (TPP) as a crosslinker, with a systematic variation in chitosan concentration, pH, TPP ratio, and stirring time to create a library of 15 formulations. Each formulation was prepared in both suspended and lyophilized forms to assess the influence of storage conditions on nanoparticle stability and performance.
The nanoparticles were evaluated through a comprehensive set of physicochemical characterization techniques including dynamic light scattering (DLS), scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and zeta potential measurements. DLS analysis revealed that lower chitosan concentrations produced smaller particles with improved size distribution and colloidal stability, with formulation 0.1-C (0.1 wt% chitosan, pH 5.5, 1:3 TPP ratio, 60 min stirring) as the most promising. This formulation retained suitable size and surface charge after lyophilization. SEM confirmed spherical morphology with a diameter of ~100 nm, and FTIR spectra indicated successful ionic interaction with TPP.
In vitro release studies with methylene blue demonstrated a maximum release of only 6.18% over 92 h despite high encapsulation efficiency (96%), suggesting the system may be unsuitable for positively charged drugs. On the other hand, curcumin, a poorly water-soluble model compound, showed improved but still limited release (~11% after 24 h). Stabilization experiments revealed that 1 wt% PVA acted as a stabilizer and cryoprotectant and maintained favorable size and PDI in both suspended and lyophilized states.

Date of Award	2025
Original language	American English
Supervisor	Emilia Oueis (Supervisor)