PMID- 8269584
OWN - NLM
STAT- MEDLINE
DCOM- 19940201
LR  - 20190830
IS  - 0344-5704 (Print)
IS  - 0344-5704 (Linking)
VI  - 33
IP  - 1
DP  - 1993
TI  - Identification of vesicle properties that enhance the antitumour activity of 
      liposomal vincristine against murine L1210 leukemia.
PG  - 17-24
AB  - The influence of vesicle lipid composition, size and drug-to-lipid ratio on the 
      antitumour activity of liposomal vincristine was assessed in the murine L1210 
      ascitic leukemia model. A pH gradient-dependent entrapment procedure was used to 
      encapsulate vincristine and allowed such vesicle properties to be independently 
      varied. Free vincristine delivered i.v. at the maximum tolerated dose (2.0 mg/kg) 
      resulted in a 27.8% increase in the life span (ILS) of mice inoculated i.p. with 
      L1210 cells. Encapsulation of the drug in egg phosphatidylcholine/cholesterol 
      vesicles did not significantly increase the antitumour efficacy of vincristine 
      (ILS, 38.9%). In contrast, administration of vincristine entrapped in vesicles 
      composed of distearoylphosphatidylcholine (DSPC)/cholesterol resulted in ILS 
      values as high as 133%. This enhanced antitumour activity of the DSPC/cholesterol 
      formulations was sensitive to the size of the liposomes; increasing the vesicle 
      size from 100 nm to 1 micron decreased the ILS from 133.3% to 55.6% at a drug 
      dose of 2.0 mg/kg. Decreasing the drug-to-lipid ratio from 0.1:1 to 0.05:1 (w/w) 
      had negligible effects on the activity of liposomal vincristine; however, a 
      further decrease in the drug-to-lipid ratio to 0.01:1 (w/w) decreased the 
      antitumour potency at all drug doses studied. Pharmacology studies indicated that 
      the antitumour activities of free and various liposomal forms of vincristine 
      correlated well with the residence time of the drug in the circulation. These 
      studies indicate that efforts to enhance the therapeutic activity of vincristine 
      through liposome encapsulation must address not only the circulation lifetime of 
      the vesicle systems but also the capacity of the liposomes to retain entrapped 
      drug in vivo.
FAU - Mayer, L D
AU  - Mayer LD
AD  - Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, 
      Canada.
FAU - Nayar, R
AU  - Nayar R
FAU - Thies, R L
AU  - Thies RL
FAU - Boman, N L
AU  - Boman NL
FAU - Cullis, P R
AU  - Cullis PR
FAU - Bally, M B
AU  - Bally MB
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Cancer Chemother Pharmacol
JT  - Cancer chemotherapy and pharmacology
JID - 7806519
RN  - 0 (Drug Carriers)
RN  - 0 (Liposomes)
RN  - 0 (Phosphatidylcholines)
RN  - 5J49Q6B70F (Vincristine)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EAG959U971 (1,2-distearoyllecithin)
SB  - IM
MH  - Animals
MH  - Cholesterol/administration & dosage
MH  - Drug Carriers
MH  - Leukemia L1210/blood/*drug therapy/mortality
MH  - Liposomes
MH  - Mice
MH  - Mice, Inbred DBA
MH  - Neoplasm Transplantation
MH  - Phosphatidylcholines/administration & dosage
MH  - Survival Rate
MH  - Vincristine/*administration & dosage/blood/therapeutic use
EDAT- 1993/01/01 00:00
MHDA- 1993/01/01 00:01
CRDT- 1993/01/01 00:00
PHST- 1993/01/01 00:00 [pubmed]
PHST- 1993/01/01 00:01 [medline]
PHST- 1993/01/01 00:00 [entrez]
AID - 10.1007/BF00686017 [doi]
PST - ppublish
SO  - Cancer Chemother Pharmacol. 1993;33(1):17-24. doi: 10.1007/BF00686017.