ETD

• aerodynamic performance
• biodegradable
• chemical composition
• chitosan
• Cystic fibrosis
• Molecular Imprinting Technology
• morphology
• nano-in-micro
• nanoparticles
• PLGA microparticles
• pulmonary drug targeting
• specific binding sites
• thermal behavior

Cystic fibrosis is an autosomal recessive genetic disease caused by mutations in the CFTR gene. These mutations compromise ion transport, leading to the production of viscous and dehydrated mucus secretions. At the pulmonary level, this causes airway obstruction, chronic inflammation, and recurrent infections, resulting in a progressive decline in respiratory function. Current management is hindered by high treatment costs, limited efficacy for specific genetic variants, and the challenge of delivering drugs through the dense mucosal barrier.
This thesis proposes an innovative strategy for pulmonary drug targeting based on biodegradable chitosan nanoparticles engineered through Molecular Imprinting Technology. Unlike traditional delivery systems, these nanoparticles are designed to act as localized “molecular traps” within the lung. By incorporating imprints specific to a target molecule, the nanoparticles sequester and concentrate drugs administred through systemic routes, thereby increasing local bioavailability while minimizing systemic exposure.
The nanoparticles were synthesized through ionotropic gelation using chitosan as the polymeric matrix and citric acid as a biocompatible and metabolizable crosslinking agent. This strategy creates specific binding sites for the template drug within the matrix. Control particles (non-imprinted) were prepared under identical conditions to verify the “recognition” effect of the molecular imprinting. To ensure suitability for inhalation, the nanoparticles were incorporated into PLGA microparticles, resulting in “nano-in-micro” structures with size, morphology, and aerodynamic properties compatible with dry powder inhaler administration. The developed systems were extensively characterized in terms of morphology, chemical composition, thermal behavior, and aerodynamic performance, alongside molecular recognition studies to confirm their “recall” capability, in vitro degradation tests at physiological pH value, and cytocompatibility evaluations.