Abstract

New lipophilic cis-platinum analogues that are non-nephrotoxic and have a broader spectrum of antitumor activity will be synthesized and formulated entrapped in liposomes of different composition and size. The toxicity, pharmacology, tumor uptake, cellular effect and antitumor activity of a few prototype liposomal-platinum preparations will be studied and compared with those of cis-platinum, the most promising second and third generation platinum complexes, and the non-entrapped compounds. The evaluation of liposomal-platinum for the targeted therapy of liver and lung metastases will receive particular attention. The cellular mechanisms involved in the increased cytotoxicity of liposomal-platinum will be studies in human cell lines sensitive and resistant to platinum derivatives. The study will define the potential clinical application of liposomes as carriers of platinum complexes and will result in the development of liposomal-platinum preparations for clinical use. The information generated will be essential in improving the design and use of drug carriers for antitumor agents.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA045423-01A3
Application #
3188516
Study Section
Experimental Therapeutics Subcommittee 2 (ET)
Project Start
1989-07-01
Project End
1992-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
1
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
University of Texas MD Anderson Cancer Center
Department
Type
Hospitals
DUNS #
001910777
City
Houston
State
TX
Country
United States
Zip Code
77030

  Publications

Sampedro, F; Partika, J; Santalo, P et al. (1994) Liposomes as carriers of different new lipophilic antitumour drugs: a preliminary report. J Microencapsul 11:309-18
Perez-Soler, R; Francis, K; al-Baker, S et al. (1994) Preparation and characterization of liposomes containing a lipophilic cisplatin derivative for clinical use. J Microencapsul 11:41-54
Han, I; Ling, Y H; Khokhar, A R et al. (1994) Cell death and DNA fragmentation induced by liposomal platinum(II) complex, L-NDDP in A2780 and A2780/PDD cells. Anticancer Res 14:421-6
Perez-Soler, R; Han, I; al-Baker, S et al. (1994) Lipophilic platinum complexes entrapped in liposomes: improved stability and preserved antitumor activity with complexes containing linear alkyl carboxylato leaving groups. Cancer Chemother Pharmacol 33:378-84
Han, I; Ling, Y H; al-Baker, S et al. (1993) Cellular pharmacology of liposomal cis-bis-neodecanoato-trans-R,R-1,2-diaminocyclohexaneplatinum(II) in A2780/S and A2780/PDD cells. Cancer Res 53:4913-9
Perez-Soler, R; Khokhar, A R (1992) Lipophilic cisplatin analogues entrapped in liposomes: role of intraliposomal drug activation in biological activity. Cancer Res 52:6341-7
Khokhar, A R; al-Baker, S; Perez-Soler, R (1992) Toxicity and efficacy studies on a series of lipid-soluble dineodecanoato(trans-R,R- and trans-S,S-1,2-diaminocyclohexane) platinum (II) complexes entrapped in liposomes. Anticancer Drugs 3:95-100
Sugarman, S M; Perez-Soler, R (1992) Liposomes in the treatment of malignancy: a clinical perspective. Crit Rev Oncol Hematol 12:231-42
Vadiei, K; Siddik, Z H; Khokhar, A R et al. (1992) Pharmacokinetics of liposome-entrapped cis-bis-neodecanoato-trans-R,R-1,2-diaminocyclohexane platinum(II) and cisplatin given i.v. and i.p. in the rat. Cancer Chemother Pharmacol 30:365-9
al-Baker, S; Perez-Soler, R; Khokhar, A R (1992) Synthesis and biological studies of new lipid-soluble cisplatin analogues entrapped in liposomes. J Inorg Biochem 47:99-108

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