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Development of liposomal formulations for pulmonary delivery with jet nebulizers has vast potential for future aerosol therapies. Different variables determine the therapeutic efficacy of aerosols, including formulation. The purpose of this study was to develop concentrated, high dose liposomal formulations initially using immunosuppressive (cyclosporin A, CsA) and anti-inflammatory drugs (budesonide, Bud) for targeted pulmonary delivery with maximal aerosol output and particle size ranges within the optimal range of 1–13 μm mass median aerodynamic diameter (MMAD). Results indicate that with increasing drug-liposome concentrations there is reduced nebulized mass output but an inversely proportional increase in aerosol output of liposomes up to critical starting concentration ranges of 21.3 mg CsA:160 mg 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC)/ml and Bud 12.5 mg:187.5 mg DLPC/ml. Above these concentration ranges (which were unique for each formulation tested), there was a reduction in the liposome aerosol output. With the increased liposome concentrations, there was a linear increase in the apparent viscosity and reduction in apparent surface tension, however, there were no demonstrable correlations between these parameters and drug output rates. Aerosol particle size analysis demonstrated that the MMAD increased minimally with higher liposome concentrations. The size range of these high dose drug-liposome aerosols is optimal for penetration into the lung periphery. |
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