Drug-biomolecule interactions: interaction of gentamicin with lipid monomolecular films.
The interaction of gentamicin with monomolecular films of a series of biologically important lipids spread on an aqueous buffered subphase was studied. The surface pressure, pi, of these films was determined by the Wilhelmy plate method as a function of surface area, A, and pi-A curves were constructed. Changes in the pi-A characteristics in the presence of gentamicin were used as a measure of antibiotic-film interaction. No interaction was observed between gentamicin and films of cholesterol, egg lecithin, dipalmitoyl lecithin, phosphatidyl ethanolamine, stearyl alcohol, and bovine ceramides at all pH values studied. Stearic acid films showed no interaction with gentamicin at pH 5. At pH 7 and 8, a small increase in pressure (approximately 3 dynes/cm) was noted. A dramatic increase in surface pressure was observed in the presence of stearyl aldehyde films ranging from approximately 9 dynes/cm at pH 7,2 to 23 dynes/cm at pH 8.4. This effect was attributed to a Schiff-base reaction between the nonprotonated primary amino groups on the gentamicin molecule and the stearyl aldehyde. Further evidence was reported by the fact that the addition of glucose (which has been reported to participate in Schiff-base formation with amines) to the subphase inhibited the stearyl aldehyde-gentamicin interaction. Sucrose did not show a corresponding effect. The addition of sodium bisulfite, which reacts with aldehydes to form alpha-hydroxysulfonic acid, also inhibited the gentamicin-stearyl aldehyde interaction. It is postulated that Schiff-base formation is a step in the in vivo transport of gentamicin across the membrane of sensitive organisms.
D055598:Chemical Phenomena; D002621:Chemistry; D002784:Cholesterol; D005839:Gentamicins; D006863:Hydrogen-Ion Concentration; D008055:Lipids; D008567:Membranes, Artificial; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D013499:Surface Properties; D013696:Temperature
D005839:Gentamicins; D008055:Lipids; D008567:Membranes, Artificial; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D002784:Cholesterol