478226 Assembling Mucus-Penetrating Antibiotic Nanoparticles from Hydrophobic Ion-Pairing Based Flashnanoprecipitation of Hydrophilic Actives

Monday, November 14, 2016
Grand Ballroom B (Hilton San Francisco Union Square)
Paradorn Rummaneethorn1, Hoang Lu1 and Robert K. Prud'homme2, (1)Chemical and Biological Engineering, Princeton University, Princeton, NJ, (2)Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ

There is currently no method to eradicate established pulmonary Pseudomonas aeruginosa infections among patients with cystic fibrosis. This in large part is due to the inability of antibiotics, such as polymyxin B, to penetrate thick lung mucosal layers formed by cystic fibrosis patients. FlashNanoPrecipitation (FNP) is a block-copolymer directed self-assembly technique that can encapsulate hydrophobic drugs into nanoparticles (NPs) that can carry drugs through mucosal layers. We here develop a new FNP process to encapsulate hydrophilic drugs using hydrophobic ion-pairing, where traditional FNP has been used to encapsulate strictly hydrophobic drugs. Sixteen ion-pairing reagents (IPs) were screened and used to successfully encapsulate several hydrophilic compounds and peptides, such as gentamicin and polymyxin. Ion-pair compositions can be varied to tune drug encapsulation efficiencies > 95%, and to tune drug release rates. Polymyxin B characteristic release rates vary from under five minutes to over seven days depending on the ion-pair:polymyxin encapsulation ratio, and ion-pair identity. The new mucus-penetrating FNP drug vehicles developed here creates new options for managing Pseudomonas aeruginosa pulmonary infections.

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