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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Effects of phospholipid chain length, concentration, charge, and vesicle size on pulmonary insulin absorption.

PURPOSE. Non drug loaded lipid vesicles have been investigated as promoters of pulmonary insulin absorption. METHODS. Physical mixtures of liposomes with insulin were delivered intratracheally to rats by direct instillation method at an insulin dose level of 1 U/kg. RESULTS. The overall hypoglycemic response, represented by area above the curve (AAC), correlated linearly with the lipid concentration for both the neutral and charged liposome-insulin preparations. The strongest response was observed with the positively charged liposomes followed by negatively charged and neutral liposome-insulin mixtures. Further toxicological studies indicated that charge-inducing agents, i.e., stearylamine and dicetylphosphate, can cause apparent disruption of pulmonary epithelial cells. From the difference of overall hypoglycemic response (AAC) among various formulations, it appears that the stronger hypoglycemic effect following positively charged liposome-insulin mixture is due to the membrane destabilizing effect on stearylamine. Optimum hypoglycemic effect was observed with a medium acyl-chain lipid (C10). The cumulative hypoglycemic response appeared to correlate inversely with the acyl carbon number of the phospholipid component from C10 to C18. The overall hypoglycemic effect does not appear to change within the liposomal size range of 0.1 micron - 1.98 microns, indicating that insulin absorption following intratracheal instillation is independent of the vesicle size within the range studied. CONCLUSIONS. Phospholipid promoted insulin pulmonary absorption is significantly dependent on the concentration, charge and acyl chain length of the phospholipids.[1]


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