A micro- and nano-structured drug carrier based on biocompatible, hybrid polymeric nanoparticles for potential application in dry powder inhalation therapy

We herein describe the development of a micro-scale powder containing hybrid polymeric nanoparticles, for pulmonary application. The nanoparticles, composed of chitosan, carboxy methyl-β-cyclodextrin and a gelling counterion, were prepared, by ionotropic gelation, and characterized using differential scanning calorimetry and infrared spectroscopy besides other techniques. Nanoparticles transformation into powders was achieved, by co-spray drying with thermo-protectant, resulting in microspheres with adequate aerodynamic properties. Besides morphological and aerodynamic analysis, the developed powder was subjected to in-depth profiling of surface composition, using X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectroscopy for investigating nanoparticles spatial distribution. After fluorescent labelling of both nanoparticles and microsphere matrix, confocal microscopic examination was further performed, for structure analysis. Overall, the applied analytical techniques evidence the homogeneous and almost complete encapsulation of the nanoparticles within microspheresʹ matrix, emphasizing the efficiency of the microencapsulation method and the potential of the hybrid nanoparticles, as a solid formulation, for lung delivery.