Antitumor activity of vincristine encapsulated in glucuronide-modified long-circulating liposomes in mice bearing Meth A sarcoma.

Abstract

Liposomes modified with the uronic acid derivative palmityl-D-glucuronide (PGlcUA) have a long circulation time and tend to accumulate in the tumors of tumor-bearing mice. Taking advantage of this character, we investigated the therapeutic effect of vincristine (VCR) encapsulated in liposomes containing PGlcUA (dipalmitoylphosphatidylcholine/cholesterol/PGlcUA = 4:4:1 as a molar ratio) on tumor-bearing mice. VCR was loaded into liposomes by a remote loading method, and then free or liposomal VCR was injected intravenously into BALB/c mice bearing Meth A sarcoma implanted subcutaneously 5 days before hand. Single-dose administration of VCR (3.0 mg/kg) in PGlcUA-liposomes significantly suppressed tumor growth, and prolonged the survival time (T/C = 1.37). Furthermore, two-dose administration of the liposomes cured one third of the animals. The therapeutic effect of PGlcUA-liposomes was greater than that of control liposomes containing dipalmitoylphosphatidylglycerol instead of PGlcUA. PGlcUA-liposomes might thus be a useful tool for delivering antitumor agents to tumor tissues.

• Authors: Y Tokudome, N Oku, K Doi, Y Namba, S Okada
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1279 Issue 1 Pg. 70-4 (Feb 21 1996) ISSN: 0006-3002 [Print] Netherlands
• PMID: 8624364 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Drug Carriers
• Glucuronates
• Liposomes
• Vincristine

Topics

• Animals
• Antineoplastic Agents, Phytogenic (administration & dosage)
• Drug Carriers
• Glucuronates
• Liposomes
• Male
• Mice
• Mice, Inbred BALB C
• Sarcoma, Experimental (drug therapy)
• Tissue Distribution
• Vincristine (administration & dosage, pharmacokinetics)