In vitro and in vivo stability of new multilamellar vesicles.
Factors affecting multilamellar vesicles transport to the blood compartment after oral administration to rats were evaluated first in vitro. A high entrapment of protein A was obtained when the vesicles were prepared by shearing a lyotropic lamellar phase composed of soybean phosphatidylcholine, cholesterol and polyoxyethylene alcohol (C12H25(OCH2CH2)4OH) as neutral detergent. In vitro tests showed that these vesicles (spherulites) were stabled in 50% of fetal calf serum, in acidic (pH 3) or basic (pH 10) buffers, in pancreatin but are partially lysed in 20mM bile salts. Oral administration of spherulites entrapping 111In-NTA in fasting rats showed a increase of radioacticivity in blood. This could be explained by passage of some spherulites in the enterocytes.
Freund
O
O
Laboratoire LEMI, Martillac, France. olivier.freund@libertysurf.fr
Amédee
J
J
Roux
D
D
Laversanne
R
R
D000284:Administration, Oral; D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism; D004064:Digestive System / Q000378:metabolism; D004337:Drug Carriers; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D007205:Indium Radioisotopes / Q000008:administration & dosage / Q000378:metabolism; D007408:Intestinal Absorption; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D010194:Pancreatin / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000737:chemistry / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D013205:Staphylococcal Protein A / Q000008:administration & dosage* / Q000378:metabolism; D013314:Stress, Mechanical
D001647:Bile Acids and Salts; D004337:Drug Carriers; D007205:Indium Radioisotopes; D008081:Liposomes; D010713:Phosphatidylcholines; D013205:Staphylococcal Protein A; D011092:Polyethylene Glycols; D010194:Pancreatin; D002784:Cholesterol