(198p) Evaluation of Mucus-Penetrating Nanocomposite Microparticles for Cystic Fibrosis-Related Infections

Cystic Fibrosis (CF) is one of the most common life-shortening genetic diseases, affecting more than 70,000 individuals worldwide. The median life expectancy of a patient born with CF in the U.S. is only 37 years. CF is characterized by the presence of abnormally thick and sticky mucus in the lungs and the impairment of the mucociliary clearance, which promotes persistent chronic pulmonary infections, in particular with Pseudomona aeruginosaas a common pathogen. The formation of biofilms is thought to protect the bacteria against antibiotic treatment, promoting drug resistance and necessitating the development of multiple antibacterial treatment options. Inhaled pulmonary delivery offers the advantage of a higher local concentration of the drug and reduced systemic side effects, as compared to those seen in oral and IV formulations. The design of PEG-coated nanoparticles offers mucus-penetrating properties that enhance their efficacy against the recurrent bacterial infections seen in CF.

The objective of this study was to develop and evaluate the efficacy of mucus-penetrating nanocomposite microparticles (nCmP) for CF-related infections, delivered via a dry powder inhaler. Polyvinyl alcohol (PVA) and Vitamin E conjugated to 5kDa poly (ethylene glycol) (VP5K) coated polymeric nanoparticles (NP) were synthesized via single emulsion using acetalated dextran (Ac-Dex), a biodegradable and tunable polymer. Both formulations resulted in spherical, smooth, highly homogeneous nanoparticles with a diameter of ~200 nm and a slightly negative ζ potential. The nCmP were produced via spray drying and preliminary characterization showed optimal size and distribution throughout the lungs, evaluated by a Next Generation Impactor (NGI).

Experiments are ongoing, with the primary objective of comparing VP5K and PVA NP to determine their mucus-penetrating properties in artificial mucus and their particle transport rates via particle tracking analysis. Curcumin is used as a drug model because of its fluorescence and known antibacterial properties. Secondary outcomes for this study will include antibacterial efficacy against P. aeruginosa PA01, a common microbe seen in CF-related pulmonary infections. Overall, VP5K-loaded-NP are a promising alternative for rapid diffusion through the mucus barrier, to release the antibiotic for treatment of P. aeruginosainfection in CF patients.