Synthesis and Characterization of Nanocomposite Microparticles (nCmP) for the Treatment of Cystic Fibrosis-Related Infections
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Pulmonary antibiotic delivery is recommended as maintenance therapy for cystic fibrosis (CF) patients who experience chronic infections. However, abnormally thick and sticky mucus present in the respiratory tract of CF patients impairs mucus penetration and limits the efficacy of inhaled antibiotics. To overcome the obstacles of pulmonary antibiotic delivery, we have developed nanocomposite microparticles (nCmP) for the inhalation application of antibiotics in the form of dry powder aerosols.
Azithromycin-loaded and rapamycin-loaded polymeric nanoparticles (NP) were prepared via nanoprecipitation and nCmP were prepared by spray drying and the physicochemical characteristics were evaluated.
The nanoparticles were 200 nm in diameter both before loading into and after redispersion from nCmP. The NP exhibited smooth, spherical morphology and the nCmP were corrugated spheres about 1 μm in diameter. Both drugs were successfully encapsulated into the NP and were released in a sustained manner. The NP were successfully loaded into nCmP with favorable encapsulation efficacy. All materials were stable at manufacturing and storage conditions and nCmP were in an amorphous state after spray drying. nCmP demonstrated desirable aerosol dispersion characteristics, allowing them to deposit into the deep lung regions for effective drug delivery.
The described nCmP have the potential to overcome mucus-limited pulmonary delivery of antibiotics.
KEY WORDScystic fibrosis nanocomposite microparticles pulmonary delivery spray drying
Cystic fibrosis transmembrane conductance regulator
Fine particle dose
Fine particles fraction
Poly(ethylene glycol) methyl ether
Next Generation Impactor
Powder X-ray diffraction
2-methoxypropene (2-MOP), triethylamine
poly(ethylene glycol) vitamin E
Acknowledgments And Disclosures
The authors gratefully acknowledge financial support from an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20GM103430. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors thank RI-INBRE for HPLC access and RIN2 for SEM, DLS, PXRD, and DSC access.
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