RT Journal Article
SR Electronic
T1 Binding of Daunomycin to Acidic Phospholipids
JF PDA Journal of Pharmaceutical Science and Technology
JO PDA J Pharm Sci Technol
FD Parenteral Drug Association (PDA)
SP 213
OP 219
VO 43
IS 5
A1 Hans Schreier
YR 1989
UL http://journal.pda.org/content/43/5/213.abstract
AB Apparent binding affinity and capacity of daunomycin to the acidic phospholipids cardiolipin, phosphatidylglycerol, phosphatidic acid, phosphatidylserine and phosphatidylinositol, and the neutral zwitterion phosphatidylcholine were estimated via extraction of the drug with and without lipids into the organic phase of a biphasic organic-aqueous system (Folch) at various pH values. Total extraction was highest at pH 8.50 (≈70% of total drug at 1 μ mole/3.6 mL concentration), medium at pH 2.77 (≈50%) and lowest at pH 6.55 (≈20%). Extraction was highly specific in the presence of all phospholipids except phosphatidylcholine at pH 6.55, and specific for cardiolipin and phosphatidylglycerol at pH 2.77. However, there was no phospholipid-specific extraction at pH 8.50. Apparent binding affinity decreased in the order phosphatidic acid » phosphatidylserine > phosphatidylinositol > phosphatidylglycerol » cardiolipin. No specific extraction was detectable in the presence of the zwitterionic phosphatidylcholine. However, cardiolipin was the only phospholipid with two binding sites per daunomycin molecule, whereas all others have only one binding site per daunomycin molecule.