This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Mayhew, E. Articles by Dave, C. Search for Related Content PubMed PubMed Citation Articles by Mayhew, E. Articles by Dave, C.

Inhibition of Tumor Cell Growth in Vitro and in Vivo by 1-ß-D-Arabinofuranosylcytosine Entrapped within Phospholipid Vesicles¹

Departments of Experimental Pathology [E. M., D. P.], and Medicine A [Y. M. R.] and Grace Cancer Drug Center [Y. M. R., C. D.], Roswell Park Memorial Institute, Buffalo, New York 14263

Phospholipid vesicles have been used as a carrier vehicle to enhance the cytotoxic activity of 1-ß-D-arabinofuranosylcytosine (ara-C) and 1-ß-D-arabinofuranosylcytosine 5'-triphosphate against several tumor cell lines. The activity of both compounds in free solution or entrapped within phospholipid vesicles was compared against L1210 cells, Ehrlich ascites cells, and SV40-transformed 3T3 cells in vitro. In addition, the activity of vesicle-entrapped ara-C against L1210 cells was also studied in vivo. The results obtained in vitro with ara-C indicated no difference in the concentration needed to inhibit growth of cells by 50% between free ara-C and vesicle-entrapped ara-C. In contrast, 1-ß-D-arabinofuranosylcytosine 5'-triphosphate entrapped in phospholipid vesicles was a more potent inhibitor of L1210 in culture (ID₅₀, 2 x 10^-8 M) compared to the relatively inactive free 1-ß-D-arabinofuranosylcytosine 5'-triphosphate (ID₅₀, >10^-7 M). Experiments carried out with L1210 cells in mice showed that, after a single i.p. dose (10 mg/kg) of vesicle-entrapped ara-C, the average survival times of mice inoculated with 10⁵ L1210 cells were increased by over 90%. In control experiments, free ara-C or vesicles plus free ara-C (10 mg/kg) did not prolong survival of mice.

¹ Supported by USPHS Research Grant CA-18524 from the National Cancer Institute.

Received 4/26/76. Accepted 8/25/76.