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Role of liposome type and route of administration in the antitumor activity of liposome-entrapped 1-beta-D-arabinofuranosylcytosine against mouse L1210 leukemia.
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1979
Year
Proteinlipid InteractionAntitumor ActivityMultilamellar VesiclesSmall Unilamellar VesiclesExtracellular MicrovesiclesLiposome TypeLipid MovementNet Surface ChargeAnti-cancer AgentCancer ResearchPharmacologyCell BiologyLipid PreparationDrug TargetingMouse L1210 LeukemiaCell SystemsVesicle BiologyLipid ChemistryMedicineCellular Biochemistry
Abstract Studies were undertaken to evaluate the antitumor activity of 1-β-d-arabinofuranosylcytosine (ara-C) entrapped in liposomes of different size and net surface charge. Liposomes were composed of phosphatidylcholine and cholesterol mixed with either phosphatidylserine (negative charge) or stearylamine (positive charge). Multilamellar vesicles were much more effective in trapping ara-C than were small unilamellar vesicles. Irrespective of liposome size, ara-C entrapped in positively charged liposomes was slightly more effective in inhibiting the growth of mouse leukemia L1210 cells in culture compared to free ara-C or ara-C entrapped in negatively charged liposomes. The results in vivo indicate that: ( a ) multilamellar vesicles containing ara-C were more effective than were small or large unilamellar vesicles composed of pure phosphatidylserine against L1210 tumors at comparable doses; ( b ) the antitumor activity of the type of large unilamellar vesicles used was limited by host toxicity; ( c ) positively and negatively charged multilamellar vesicles were equally effective in vivo ; ( d ) entrapped ara-C was effective against L1210 tumors at both 10 5 and 10 6 initial tumor load; ( e ) entrapped ara-C was active against L1210 tumors when tumor transplant and treatment were both carried out by the i.v. route; ( f ) mice treated p.o. with entrapped ara-C showed increased survival times; and ( g ) acute toxicity tests in mice indicated that for liposomes without the drug the dose lethal to 50% of the mice was greater than 5 g/kg (total lipid per body weight). The same tests indicated that encapsulated ara-C was more toxic than was the free drug. The mechanisms of the antitumor action of liposome-entrapped ara-C are not clear, and the evidence could be explained by some type of “depot” system without any assumption of a specific delivery system to tumor cells.