BACKGROUND: Swellable hydrogel microparticle-based pressurized metered dose inhaler (pMDI) formulations allow delivery of small respirable sized particles (1-5 microns), which swell upon the deposition in the deep lung and therefore can elude alveolar macrophage uptake via their larger geometric sizes. In addition, optimized surface chemistry may allow for sustained release of drug for multiple days. METHODS: Drug-loaded PLGA nanoparticles encapsulated in PEG/chitosan (Cs) graft copolymer-based hydrogel microparticles were synthesized and characterized. Physical stability of dispersions within Hydrofluoroalkane propellant systems was assessed. The formulations were evaluated for aerosolization performance using a Next Generation Impactor. RESULTS: Low density PEG/chitosan (Cs) graft copolymer-based hydrogel microparticles containing drug-loaded PLGA nanoparticles has an average diameter of 1-2 μm. These dispersions showed good compatibility with HFA227ea. Suspension stability was found to vary with the concentration of hydrogel particles. It was typically between 1 to 5 min and was found to be easily redispersible. Aerosolization studies showed fine particle fraction as high as 65% could be achieved. CONCLUSIONS: These swellable hydrogel-based microparticle pMDI formulations could be used as potential delivery vehicles for nanoparticle therapeutics.
BACKGROUND: Swellable hydrogel microparticle-based pressurized metered dose inhaler (pMDI) formulations allow delivery of small respirable sized particles (1-5 microns), which swell upon the deposition in the deep lung and therefore can elude alveolar macrophage uptake via their larger geometric sizes. In addition, optimized surface chemistry may allow for sustained release of drug for multiple days. METHODS: Drug-loaded PLGA nanoparticles encapsulated in PEG/chitosan (Cs) graft copolymer-based hydrogel microparticles were synthesized and characterized. Physical stability of dispersions within Hydrofluoroalkane propellant systems was assessed. The formulations were evaluated for aerosolization performance using a Next Generation Impactor. RESULTS: Low density PEG/chitosan (Cs) graft copolymer-based hydrogel microparticles containing drug-loaded PLGA nanoparticles has an average diameter of 1-2 μm. These dispersions showed good compatibility with HFA227ea. Suspension stability was found to vary with the concentration of hydrogel particles. It was typically between 1 to 5 min and was found to be easily redispersible. Aerosolization studies showed fine particle fraction as high as 65% could be achieved. CONCLUSIONS: These swellable hydrogel-based microparticle pMDI formulations could be used as potential delivery vehicles for nanoparticle therapeutics.