(681e) Nanoparticle-Stabilized Colloids in Compressible Hydrofluoroalkanes

Hydrofluoroalkanes (HFAs) are the propellants of choice in a broad range of industrial applications, including medical sprays such as pressurized metered-dose inhalers (pMDIs).  pMDIs are of relevance in the context of oral inhalation (OI) therapies as they are the least expensive and most widely used devices for the regional delivery of drugs to the lungs.  The potential of pMDIs is much broader, however, as the lungs are also recognized as an efficient pathway for both small molecular weight drugs and therapeutic biomacromolecules to the blood stream.  However, most therapeutics have limited solubility in HFAs, due to their dual hydrophobic and at the same time lipophobic character, typically requiring the formulation of drugs as colloidal dispersions, or the use of co-solvents to enhance drug solubility for the formulation of solution pMDIs.

In this work we show that nanoparticles (NPs) dispersed in compressible hydrofluoroalkanes (HFAs) at small volume fractions are capable of stabilizing micron-sized particle colloids, which otherwise flocculate due to strong van der Waals forces.  Water-soluble, biodegradable NPs with a chitosan (CS) core, grafted with highly HFA-philic moieties can be readily dispersed in the low dielectric HFAs, and are capable of imparting stability to a wide range of therapeutic particles having different chemistries (polar or hydrophobic; small and large molecular weight, including peptides and proteins) and morphologies (micronized crystals or amorphous), and producing aerosols conducive to deep lung deposition.  These NP systems thus serve as a broadly applicable platform for the non-invasive delivery of therapeutics to and through the lungs using propellant-based, portable inhalers, and are also of potential relevance in other industries where HFAs are employed as solvents or propellants.  This concept may also be applicable to other compressible solvents.