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Biomedical subjects

D Papahadjopoulos

Publications and source records attributed to D Papahadjopoulos.

198 records · Page 11Linked to original sources
PubMed1969

Stability of asymmetric phospholipid membranes.

Bilayers (black films) composed of phosphatidylserine are unstable under conditions of asymmetric distribution of calcium or hydrogen ions with respect to the membrane. Addition of calcium ions to the solution (100 millimolar sodium chloride, pH 7.0) on one side only, produces lowering of the direct-current resistance and results in breaking of the membrane. However, with calcium ions on both sides the membranes are stable and show very high electrical resistance.

Calcium↗
PubMedDate not supplied

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism.

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.

Animals↗
PubMedDate not supplied

Retention of cytosine arabinoside in mouse lung following intravenous administration in liposomes of different size.

An extrusion technique was used to obtain multilamellar lipid vesicles (MLV, liposomes) of different size distribution. The larger MLV ranged in diameter from 0.1 to 2.6 mu and the smaller from 0.1 to 1.5 mu, and both were composed of phosphatidylserine/phosphatidylcholine/cholesterol in the molar ratio 1:4:5. After intravenous injection of large and small MLV containing encapsulated [3H]cytosine arabinoside (ara-C), their distribution in various organs showed that the fraction of the dose associated with lung was greater for large MLV relative to small MLV by factors of 3.6--10 after 1 hr, 5.3--14 after 4 hr, and 17--23 after 24 hr. For large MLV more than 50% of drug remaining in vivo after 24 hr was associated with the lung, compared with 2.5% for small MLV. Almost all of the 3H associated with lung at all times for both large and small MLV could be accounted for by unchanged ara-C. Differences in 3H levels between small and large MLV in other tissues were much less dramatic or were not significant. The apparent in vivo stability of the liposomes was not affected by size. The data are consistent with an initial trapping of large MLV during first passage in the lung, with subsequent binding and retention. Release of ara-C from large or small MLV in the lung is apparently slow relative to meatbolism.

Animals↗