The modulation of a variety of mechanisms of channel-mediated transport across unilamellar phospholipid membranes by a range of halogenated inhalation general anaesthetics (chloroform, enflurane, halothane and methoxyflurane) was investigated using 1H-NMR spectroscopy. Transport of the probe ion Pr3+ across egg yolk phosphatidylcholine (PC) and dipalmitoyl phosphatidylcholine (DPPC) vesicular membranes in the presence of the channel forming polypeptides alamethicin 30 and melittin, and the polyene antibiotic nystatin, as well as the degree of vesicular lysis at the gel to liquid-crystal phase transition of DPPC vesicles was monitored. The observation that the inhalation general anaesthetics inhibit such membrane permeability independently of the channel system or type of lipid used, suggests that hydrogen-bonded water structure and/or hydrogen-bonding centres at dipolar lipid-polypeptide interfaces, can be likely sites of action of the general anaesthetics.

Anesthetics↗

PubMedDate not supplied

Application of 1H-n.m.r. to the design of liposomes for oral use. Synergistic activity of bile salts and pancreatic phospholipase A2 in the induced permeability of small unilamellar phospholipid vesicles.

H-n.m.r. spectroscopy of small unilamellar phospholipid vesicles in the presence of the lanthanide probe ion Dy3+ has been used to study the permeability of these liposomes induced by the bile salts (glycocholate and glycodeoxycholate) and pancreatic phospholipase A2. A marked synergism is demonstrated in the combined effects of these digestive agents in producing permeability of the vesicles to Dy3+. Changes in the 1H-n.m.r. spectrum of the vesicular phospholipid head-groups before permeability is induced, indicate that the products of the enzymic hydrolysis (lyso lipids and fatty acids) and transmembrane lipid exchange are involved in the permeability mechanism. The results are discussed in terms of the advantages of the use of n.m.r. techniques in the future design of liposomes for oral use.

Administration, Oral↗