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

A. R. Khokhar, S. Al-Baker, Roman Perez-Soler

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

A number of highly lipophilic dineodecanoato(trans-R,R- and trans-S,S-1,2-diaminocyclohexane) platinum (II) complexes were entrapped in multilamellar vesicles composed of dimyristoyl phosphatidylcholine and dimyristoyl phosphatidyl-glycerol at a molar ratio of 7:3. The entrapment efficiency and stability of liposomal platinum (L-Pt) preparations was > 90%. The subacute mouse LD50 of L-Pt preparations tested ranged from 60 to 104 mg/kg. All L-Pt preparations tested had no significant nephrotoxicity at the LD50 dose except for L-Pt 5, which caused renal dysfunctions (as evidenced by elevated blood urea nitrogen levels) at the LD50 dose. L-Pt preparations had shown good in vivo antitumor activity against i.p. L1210 leukemia when an optimal dose was administered i.p. to mice on days 1, 5 and 9 (% T/C 230-300; cisplatin 220). L-Pt preparations were also markedly active, by the i.p. route, against L1210 leukemia resistant to cisplatin (% T/C 237-355; cisplatin 112). All L-Pt preparations exhibited significant antitumor activity against B16 melanoma when administered i.p. on day 1 (% T/C 144-155; cisplatin 161). L-Pt 1, 3 and 5 were all tested by the i.v. route on days 4, 8 and 12 against M5076 reticulosarcoma, but none of these preparations showed any significant antitumor activity against this tumor system (% T/C 120-127; cisplatin 173). Current studies aimed at optimizing the liposomal formulation of these compounds should result in the selection of a single isomeric L-Pt formulation for clinical development.

Original languageEnglish (US)
Pages (from-to)95-100
Number of pages6
JournalAnti-Cancer Drugs
Volume3
Issue number2
StatePublished - 1992
Externally publishedYes

Fingerprint

Platinum
Liposomes
Lipids
Cisplatin
Lethal Dose 50
Leukemia L1210
((1R,2R)-1,2-diaminocyclohexane)platinum(II)
Phosphatidylglycerols
Experimental Melanomas
Blood Urea Nitrogen
Phosphatidylcholines
Non-Hodgkin's Lymphoma
Kidney

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pharmacology

Cite this

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title = "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",
abstract = "A number of highly lipophilic dineodecanoato(trans-R,R- and trans-S,S-1,2-diaminocyclohexane) platinum (II) complexes were entrapped in multilamellar vesicles composed of dimyristoyl phosphatidylcholine and dimyristoyl phosphatidyl-glycerol at a molar ratio of 7:3. The entrapment efficiency and stability of liposomal platinum (L-Pt) preparations was > 90{\%}. The subacute mouse LD50 of L-Pt preparations tested ranged from 60 to 104 mg/kg. All L-Pt preparations tested had no significant nephrotoxicity at the LD50 dose except for L-Pt 5, which caused renal dysfunctions (as evidenced by elevated blood urea nitrogen levels) at the LD50 dose. L-Pt preparations had shown good in vivo antitumor activity against i.p. L1210 leukemia when an optimal dose was administered i.p. to mice on days 1, 5 and 9 ({\%} T/C 230-300; cisplatin 220). L-Pt preparations were also markedly active, by the i.p. route, against L1210 leukemia resistant to cisplatin ({\%} T/C 237-355; cisplatin 112). All L-Pt preparations exhibited significant antitumor activity against B16 melanoma when administered i.p. on day 1 ({\%} T/C 144-155; cisplatin 161). L-Pt 1, 3 and 5 were all tested by the i.v. route on days 4, 8 and 12 against M5076 reticulosarcoma, but none of these preparations showed any significant antitumor activity against this tumor system ({\%} T/C 120-127; cisplatin 173). Current studies aimed at optimizing the liposomal formulation of these compounds should result in the selection of a single isomeric L-Pt formulation for clinical development.",
author = "Khokhar, {A. R.} and S. Al-Baker and Roman Perez-Soler",
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T1 - 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

AU - Khokhar, A. R.

AU - Al-Baker, S.

AU - Perez-Soler, Roman

PY - 1992

Y1 - 1992

N2 - A number of highly lipophilic dineodecanoato(trans-R,R- and trans-S,S-1,2-diaminocyclohexane) platinum (II) complexes were entrapped in multilamellar vesicles composed of dimyristoyl phosphatidylcholine and dimyristoyl phosphatidyl-glycerol at a molar ratio of 7:3. The entrapment efficiency and stability of liposomal platinum (L-Pt) preparations was > 90%. The subacute mouse LD50 of L-Pt preparations tested ranged from 60 to 104 mg/kg. All L-Pt preparations tested had no significant nephrotoxicity at the LD50 dose except for L-Pt 5, which caused renal dysfunctions (as evidenced by elevated blood urea nitrogen levels) at the LD50 dose. L-Pt preparations had shown good in vivo antitumor activity against i.p. L1210 leukemia when an optimal dose was administered i.p. to mice on days 1, 5 and 9 (% T/C 230-300; cisplatin 220). L-Pt preparations were also markedly active, by the i.p. route, against L1210 leukemia resistant to cisplatin (% T/C 237-355; cisplatin 112). All L-Pt preparations exhibited significant antitumor activity against B16 melanoma when administered i.p. on day 1 (% T/C 144-155; cisplatin 161). L-Pt 1, 3 and 5 were all tested by the i.v. route on days 4, 8 and 12 against M5076 reticulosarcoma, but none of these preparations showed any significant antitumor activity against this tumor system (% T/C 120-127; cisplatin 173). Current studies aimed at optimizing the liposomal formulation of these compounds should result in the selection of a single isomeric L-Pt formulation for clinical development.

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