Liposomal formulation of DIMIQ, potential antitumor indolo[2,3-b]quinoline agent and its cytotoxicity on hepatoma Morris 5123 cells.
The cytotoxic and antitumor activity of DIMIQ (5,11-dimethyl-5H-indolo[2,3-b]quinoline), synthetic analog of neocryptolepine, makes this compound a potential antitumor agent. An attempt to obtain liposomal form of DIMIQ.HCl was undertaken in the present study. Standard experimental conditions were chosen and information on the physicochemical parameters of the liposome dispersion containing studied indoloquinoline agent was collected. The effective and efficient encapsulation of DIMIQ.HCl (66.6%) in conventional liposomes (FAT-MLV, DMPC:DMPG 7:3 w/w at pH 7.0), uniformity of the size of liposomal vesicles, and high stability at pH 6.5 were demonstrated. Hemolysis of sheep erythrocytes induced by free form of DIMIQ.HCl was dramatically decreased after addition of liposome-entrapped DIMIQ.HCl. Treatment of hepatoma Morris 5123 cells for 24 hr with different concentrations of both free and its liposomal formulation of DIMIQ.HCl resulted in significant changes in cell morphology accompanied by reduction of cell viability.
Jaromin
Anna
A
Department of Lipids and Liposomes, Faculty of Biotechnology, University of Wroclaw, Wroclaw, Poland. ajaromin@ibmb.uni.wroc.pl
Kozubek
Arkadiusz
A
Suchoszek-Lukaniuk
Katarzyna
K
Malicka-Blaszkiewicz
Maria
M
Peczynska-Czoch
Wanda
W
Kaczmarek
Lukasz
L
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D002243:Carbolines / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004339:Drug Compounding; D020404:Glycerophospholipids / Q000737:chemistry*; D006461:Hemolysis / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D008081:Liposomes; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D010316:Particle Size; D010715:Phosphatidylglycerols / Q000737:chemistry; D051381:Rats; D011915:Rats, Inbred BUF; D012756:Sheep; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D002243:Carbolines; D020404:Glycerophospholipids; D008081:Liposomes; D010715:Phosphatidylglycerols; C055575:5,11-dimethyl-5H-indolo(2,3-b)quinoline; D015060:1,2-Dipalmitoylphosphatidylcholine; D004134:Dimyristoylphosphatidylcholine; C030345:1,2-dipalmitoylphosphatidylglycerol