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- W2007015807 abstract "Microspheres made of chitosan, a biodegradable polymer, were investigated as a potential carrier for therapeutic proteins, peptides and plasmid DNA for administration to the lung from a pressurized metered dose inhaler (pMDI). Through the use of different cross-linking agents and additives, the physicochemical properties of chitosan microspheres were modified to improve compatibility in a pMDI delivery system. Their density, thermal properties, surface hydrophobicity, surface charge and free amino group content were determined before and after formulation in a pMDI system utilizing P134a. Also, the in vitro delivery characteristics of the pMDI systems were ascertained by cascade impaction. The densities of the non cross-linked and the glutaraldehyde cross-linked chitosan microspheres closely matched that of liquid P134a. An increase in the median particle size and the polydispersity after exposure to P134a was found for all types of chitosan microspheres tested except for those cross-linked with glutaraldehyde. This was due to the presence of water in P134a which hydrated and plasticized the chitosan microspheres causing aggregation during storage of the pMDI formulations. The change in the mass median aerodynamic diameter (MMAD) of the emitted dose of the pMDI systems reflected the influence of water on the particle size distribution of the chitosan microsphere pMDI suspension formulations. The pMDI systems studied produced respirable fractions (%RF) of 18% and multiple determinations of the dose delivery through-the-valve (DDV) of the pMDI systems were consistent. The surface hydrophobicity of the glutaraldehyde cross-linked chitosan microspheres was significantly greater than non cross-linked or tripolyphosphate (TPP) cross-linked chitosan microspheres. The addition of aluminum hydroxide (Al(OH3)) to non cross-linked chitosan microspheres did not significantly influence the surface hydrophobicity. A decrease in the free surface amine content and the zeta potential after exposure to P134a was related to hydration and plasticization by water contained in the pMDI formulations. The non cross-linked and the glutaraldehyde cross-linked chitosan microspheres were found to be potential candidates for carrying biotherapeutic compounds to the lung via a pMDI system due to their compatability with P134a and their physicochemical characteristics." @default.
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- W2007015807 date "1998-11-01" @default.
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- W2007015807 title "Investigation of a pMDI system containing chitosan microspheres and P134a" @default.
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- W2007015807 doi "https://doi.org/10.1016/s0378-5173(98)00266-x" @default.
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