Increased plasma removal of microemulsions resembling the lipid phase of low-density lipoproteins (LDL) in patients with acute myeloid leukemia: a possible new strategy for the treatment of the disease.
A microemulsion of lipid composition resembling low-density lipoprotein (LDL), but devoid of apolipoproteins and labeled with [14C]-cholesteryl oleate was injected into 16 healthy subjects and into 15 patients with acute myeloid leukemia (AML). Removal from plasma of the lipid label was higher in the leukemic group compared to healthy subjects in terms of fractional clearance rate (0.185 +/- 0.205 and 0.080 +/- 0.030 h-1, respectively, P < 0.03). When the emulsion was again injected into 10 of the AML patients after complete hematological remission, the fractional clearance rate of cholesteryl ester was reduced to one third of the value observed prior to treatment (0.061 +/- 0.038 h-1) and was not different from that obtained for the healthy subjects. Also, in untreated AML patients, serum LDL-cholesterol levels inversely correlated with the values of fractional clearance rate of the microemulsion. This correlation was no longer observed after treatment. These data suggest that the LDL-like microemulsion was selectively taken up by the neoplastic cells presumably by interaction with LDL receptors. Therefore, microemulsions may function as potential carriers for anticancer drugs that are targeted to tumor cells for patients with acute myeloid leukemia. Unlike native LDL, microemulsions are suitable for utilization in routine clinical practice.
Maranhão
R C
RC
Instituto do Coração, Hospital das Clínicas, São Paulo, Brasil.
Garicochea
B
B
Silva
E L
EL
Llacer
P D
PD
Pileggi
F J
FJ
Chamone
D A
DA
D000208:Acute Disease; D002250:Carbon Radioisotopes; D002788:Cholesterol Esters; D004341:Drug Evaluation; D005217:Fat Emulsions, Intravenous / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000097:blood* / Q000188:drug therapy; D008055:Lipids / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood* / Q000187:drug effects; D008297:Male; D008657:Metabolic Clearance Rate; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
D002250:Carbon Radioisotopes; D002788:Cholesterol Esters; D005217:Fat Emulsions, Intravenous; D008055:Lipids; D008077:Lipoproteins, LDL; D014280:Triglycerides