Aerosolised polymyxins are used in the antimicrobial therapy of cystic fibrosis lung infections. As with other antimicrobials, PXB was rapidly cleared from the lungs of adult rats after intratracheal instillation. Lung residence time of PXB was prolonged by liposomal encapsulation and was dependent upon liposomal phospholipid composition. Formulation studies indicated that liposomal encapsulation of PXB was strongly dependent on the bilayer fluidity. Although PXB has a hydrophilic polycationic heptapeptide ring, tripeptide tail terminates in a short hydrophobic fatty acyl chain, allowing membrane penetration. Therefore after entrapment, PXB may be associated with both internal aqueous compartments and liposomal bilayers. As the site of association may influence liposomal release kinetics, the aim of this present study was to further evaluate the membrane interaction of PXB with liposomal bilayers using differential scanning calorimetry (DSC) and gel chromatography.
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