Preparation and in vitro synergistic anticancer effect of vitamin K3 and 1,8-diazabicyclo[5,4,0]undec-7-ene in poly(ethylene glycol)-diacyllipid micelles.
Polymeric micelles consisting of poly(ethylene glycol)-distearoyl phosphoethanolamine conjugates (PEG-DSPE) loaded with Vitamin K3 (VK3) to 0.2 mg of drug/mg of carrier and with 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU) to 0.06 mg of drug/mg of carrier were prepared. These micelles were stable for as long as 6 months during storage at 4 degrees C and did not change their size or release the incorporated drugs. Co-encapsulation of VK3 and DBU into PEG-DSPE micelles resulted in synergistic anticancer effects against both murine and human cancer cells in vitro. The synergism may be explained by the fact that the presence of DBU promotes the escape of drug-loaded micelles from the endosomes of cancer cells directly into the cytoplasm as demonstrated by fluorescent microscopy.
Wang
Junping
J
Department of Pharmaceutical Sciences, Bouvé College of Health Sciences, Northeastern University, Mugar Building 312, 360 Huntington Avenue, Boston, MA 02115, USA.
Mongayt
Dmitriy A
DA
Lukyanov
Anatoly N
AN
Levchenko
Tatiana S
TS
Torchilin
Vladimir P
VP
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004338:Drug Combinations; D004355:Drug Stability; D004357:Drug Synergism; D005260:Female; D006801:Humans; D051379:Mice; D008823:Micelles; D008856:Microscopy, Fluorescence; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D014407:Tumor Cells, Cultured; D024483:Vitamin K 3 / Q000737:chemistry* / Q000494:pharmacology
C487954:1,2-diastearoyl-sn-glycero-3-phosphatidylethanolamine-N-(methoxy(polyethylene glycol)3000); D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004338:Drug Combinations; D008823:Micelles; D010714:Phosphatidylethanolamines; D011092:Polyethylene Glycols; D024483:Vitamin K 3; C031033:1,8-diazabicyclo(5.4.0)undec-7-ene