Lipid-based nanoparticulate systems for the delivery of anti-cancer drug cocktails: Implications on pharmacokinetics and drug toxicities

Current Drug Metabolism

Volumn 10, Issue 8, 2009, Pages 861-874

  Chiu, Gigi N C ^a   Wong, Man Yi ^a   Ling, Leong Uung ^a   Shaikh, Ishaque M ^a   Tan, Kuan Boone ^a   Chaudhury, Anumita ^a   Tan, Bee Jen ^a  

^a NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

Author keywords

Cancer; Drug combination; Liposomes; Nanotechnology; Pharmacokinetics; Synergism

Indexed keywords

7 ETHYL 10 HYDROXYCAMPTOTHECIN; AMLODIPINE PLUS TOPOTECAN; ANNAMYCIN; ANTINEOPLASTIC AGENT; ANTISENSE OLIGONUCLEOTIDE; CARBOPLATIN PLUS FLOXURIDINE; CISPLATIN; CISPLATIN PLUS IRINOTECAN; CPX 1; CPX 351; CPX 571; CYTARABINE; CYTARABINE PLUS DAUNORUBICIN; DAUNORUBICIN; DOXORUBICIN; DOXORUBICIN PLUS IRINOTECAN; DOXORUBICIN PLUS VINCRISTINE; ENDOTAG 1; EVACET; FLOXURIDINE; FLOXURIDINE PLUS IRINOTECAN; FLURADARABINE PLUS MITOXANTRONE; INX 0125; IRINOTECAN; LE SN 38; LEM ETU; LEP ETU; LIPOPLATIN; LIPOSOMAL ANNAMYCIN; LIPOSOME; LURTOTECAN; MARQUIBO; MBT 0206; MITOXANTRONE; NAVELBINE; OXALIPLATIN; PACLITAXEL; PLATINUM 1,2 DIAMINOCYCLOHEXANE BISNEODECANOATE; QUINACRINE PLUS VINCRISTINE; RETINOIC ACID; SMALL INTERFERING RNA; UNCLASSIFIED DRUG; UNINDEXED DRUG; VERAPAMIL; VINCRISTINE;

ACUTE GRANULOCYTIC LEUKEMIA; ACUTE LYMPHOBLASTIC LEUKEMIA; B CELL LYMPHOMA; BREAST CANCER; CANCER RESISTANCE; CANCER THERAPY; CHRONIC MYELOID LEUKEMIA; CLINICAL TRIAL; COLORECTAL CANCER; DIGESTIVE SYSTEM CANCER; DRUG DELIVERY SYSTEM; DRUG MECHANISM; DRUG POTENTIATION; ENCAPSULATION; HEAD AND NECK CANCER; HUMAN; KAPOSI SARCOMA; KIDNEY CARCINOMA; LEUKEMIA; LIVER CANCER; LUNG CANCER; LYMPHOMA; MAXIMUM TOLERATED DOSE; MELANOMA; NANOTECHNOLOGY; NEOPLASM; NONHODGKIN LYMPHOMA; NONHUMAN; OVARY CANCER; OVARY TUMOR; PHARMACOKINETICS; PROMYELOCYTIC LEUKEMIA; REVIEW; SOLID TUMOR; STOMACH CANCER; TUMOR LOCALIZATION;

ANIMALS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; DRUG CARRIERS; DRUG DELIVERY SYSTEMS; DRUG RESISTANCE, NEOPLASM; DRUG SCREENING ASSAYS, ANTITUMOR; DRUGS, INVESTIGATIONAL; HUMANS; LIPOSOMES; MODELS, BIOLOGICAL; NANOPARTICLES; NEOPLASMS;

EID: 74249095292     PISSN: 13892002     EISSN: None     Source Type: Journal    
DOI: 10.2174/138920009790274531     Document Type: Review

References (175)

1. Chu, E.; DeVita, V.T.J. In Cancer:. Principles. and. practice. of. oncology. DeVita, V.T.J.; Hellman, S.; Rosenberg, S.A., Eds.; Lippincott Williams & Wilkins: Philadelphia, 2001; Vol. 1, pp. 289-306.
2. Frei, E.I.; Eder, J.P. In Cancer. Medicine. 6. Kufe, D.W.; Holland, J.F.; Frei, E.I., Eds.; B.C. Decker Inc.: Hamilton., 2003; Vol. 2, pp. 669-677.
3. Frei, E.I. In Synergism. and. antagonism. in. chemotherpy. Chou, T.C.; Rideout, D.C., Eds.; Academic Press: California, 1991, pp. 103-108.
4. Delbaldo, C.; Michiels, S.; Syz, N.; Soria, J.C.; Le Chevalier, T.; Pignon, J.P. Benefits of adding a drug to a single-agent or a 2-agent chemotherapy regimen in advanced non-small-cell lung cancer: a meta-analysis. JAMA, 2004, 292(4), 470-484.
5. Di Maio, M.; Chiodini, P.; Georgoulias, V.; Hatzidaki, D.; Takeda, K.; Wachters, F.M.; Gebbia, V.; Smit, E.F.; Morabito, A.; Gallo, C.; Perrone, F.; Gridelli, C. Meta-analysis of single-agent chemotherapy compared with combination chemotherapy as second-line treatment of advanced non-small-cell lung cancer. J. Clin. Oncol., 2009, 27(11), 1836-1843.
6. Mayer, L.D.; Harasym, T.O.; Tardi, P.G.; Harasym, N.L.; Shew, C.R.; Johnstone, S.A.; Ramsay, E.C.; Bally, M.B.; Janoff, A.S. Ratiometric dosing of anticancer drug combinations: controlling drug ratios after systemic administration regulates therapeutic activity in tumor-bearing mice. Mol. Cancer Ther., 2006, 5(7), 1854-1863.
7. Hamoudeh, M.; Kamleh, M.A.; Diab, R.; Fessi, H. Radionuclides delivery systems for nuclear imaging and radiotherapy of cancer. Adv. Drug Deliv. Rev., 2008, 60(12), 1329-1346.
8. Sajja, H.K.; East, M.P.; Mao, H.; Wang, Y.A.; Nie, S.; Yang, L. Development of multifunctional nanoparticles for targeted drug delivery and noninvasive imaging of therapeutic effect. Curr. Drug Discov. Technol., 2009, 6(1), 43-51.
9. Bangham, A.D.; Standish, M.M.; Watkins, J.C. Diffusion of univalent ions across the lamellae of swollen phospholipids. J. Mol. Biol., 1965, 13(1), 238-252.
10. Bangham, A.D. Membrane models with phospholipids. Prog. Biophys. Mol. Biol., 1968, 18, 29-95.
11. Sessa, G.; Weissmann, G. Phospholipid spherules(liposomes) as a model for biological membranes. J. Lipid Res., 1968, 9(3), 310-318.
12. Gregoriadis, G.; Wills, E.J.; Swain, C.P.; Tavill, A.S. Drug-carrier potential of liposomes in cancer chemotherapy. Lancet, 1974, 1(7870), 1313-1316.
13. Gabizon, A.; Dagan, A.; Goren, D.; Barenholz, Y.; Fuks, Z. Liposomes as in vivo carriers of adriamycin: reduced cardiac uptake and preserved antitumor activity in mice. Cancer Res., 1982, 42(11), 4734-4739.
14. Mayer, L.D. Future developments in the selectivity of anticancer agents: drug delivery and molecular target strategies. Cancer Metastasis Rev., 1998, 17(2), 211-218.
15. Mayer, L.D.; Krishna, R.; Bally, M.B. In Polymeric. biomaterials, Second edition, revised and expanded ed. Dumitriu, S., Ed.; Marcel Dekker: New York, 2001, pp. 823-841.
16. Mayer, L.D.; Tai, L.C.; Ko, D.S.; Masin, D.; Ginsberg, R.S.; Cullis, P.R.; Bally, M.B. Influence of vesicle size, lipid composition, and drug-to-lipid ratio on the biological activity of liposomal doxorubicin in mice. Cancer Res., 1989, 49(21), 5922-5930.
17. Matsumura, Y.; Maeda, H. A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res., 1986, 46(12 Pt 1), 6387-6392.
18. Yuan, F.; Leunig, M.; Huang, S.K.; Berk, D.A.; Papahadjopoulos, D.; Jain, R.K. Microvascular permeability and interstitial penetration of sterically stabilized(stealth) liposomes in a human tumor xenograft. Cancer Res., 1994, 54(13), 3352-3356.
19. Gabizon, A.; Papahadjopoulos, D. The role of surface charge and hydrophilic groups on liposome clearance in vivo. Biochim. Biophys. Acta, 1992, 1103(1), 94-100.
20. Gabizon, A.A. Selective tumor localization and improved therapeutic index of anthracyclines encapsulated in long-circulating liposomes. Cancer Res., 1992, 52(4), 891-896.
21. Chonn, A.; Semple, S.C.; Cullis, P.R. Association of blood proteins with large unilamellar liposomes in vivo. J. Biol. Chem., 1992, 267(26), 18759-18765.
22. Scherphof, G.; Roerdink, F.; Waite, M.; Parks, J. Disintegration of phosphatidylcholine liposomes in plasma as a result of interaction with high-density lipoproteins. Biochim. Biophys. Acta, 1978, 542(2), 296-307.
23. Senior, J.; Gregoriadis, G.; Mitropoulos, K.A. Stability and clearance of small unilamellar liposomes. Studies with normal and lipoprotein-deficient mice. Biochim. Biophys. Acta, 1983, 760(1), 111-118.
24. Guo, L.S.; Hamilton, R.L.; Goerke, J.; Weinstein, J.N.; Havel, R.J. Interaction of unilamellar liposomes with serum lipoproteins and apolipoproteins. J. Lipid Res., 1980, 21(8), 993-1003.
25. Williams, K.J.; Phillips, M.C.; Rodrigueza, W.V. Structural and metabolic consequences of liposome-lipoprotein interactions. Adv. Drug Deliv. Rev., 1998, 32(1-2), 31-43.
26. Drummond, D.C.; Meyer, O.; Hong, K.; Kirpotin, D.B.; Papahadjopoulos, D. Optimizing liposomes for delivery of chemotherapeutic agents to solid tumors. Pharmacol. Rev., 1999, 51(4), 691-743.
27. Drummond, D.C.; Noble, C.O.; Hayes, M.E.; Park, J.W.; Kirpotin, D.B. Pharmacokinetics and in vivo drug release rates in liposomal nanocarrier development. J. Pharm. Sci., 2008, 97(11), 4696-4740.
28. Damen, J.; Regts, J.; Scherphof, G. Transfer and exchange of phospholipid between small unilamellar liposomes and rat plasma high density lipoproteins. Dependence on cholesterol content and phospholipid composition. Biochim. Biophys. Acta, 1981, 665(3), 538-545.
29. Senior, J.; Gregoriadis, G. Stability of small unilamellar liposomes in serum and clearance from the circulation: the effect of the phospholipid and cholesterol components. Life Sci., 1982, 30(24), 2123-2136.
30. Huang, S.K.; Mayhew, E.; Gilani, S.; Lasic, D.D.; Martin, F.J.; Papahadjopoulos, D. Pharmacokinetics and therapeutics of sterically stabilized liposomes in mice bearing C-26 colon carcinoma. Cancer Res., 1992, 52(24), 6774-6781.
31. Mayer, L.D.; Dougherty, G.; Harasym, T.O.; Bally, M.B. The role of tumor-associated macrophages in the delivery of liposomal doxorubicin to solid murine fibrosarcoma tumors. J. Pharmacol. Exp. Ther., 1997, 280(3), 1406-1414.
32. Allen, T.M.; Hansen, C.B. Pharmacokinetics of stealth versus conventional liposomes: effect of dose. Biochim. Biophys. Acta, 1991, 1068(2), 133-141.
33. Senior, J.; Delgado, C.; Fisher, D.; Tilcock, C.; Gregoriadis, G. Influence of surface hydrophilicity of liposomes on their interaction with plasma protein and clearance from the circulation: studies with poly(ethylene glycol)-coated vesicles. Biochim. Biophys. Acta, 1991, 1062(1), 77-82.
34. Papahadjopoulos, D.; Allen, T.M.; Gabizon, A.; Mayhew, K.; Huang, S.K.; Lee, L.D.; Woodle, M.C.; Lasic, D.D.; Redemann, C.; Martin, F.J. Sterically stabilized liposomes: improvements in pharmacokinetics and antitumor therapeutic efficacy. Proc. Natl. Acad. Sci. USA, 1991, 88(24), 11460-11464.
35. Allen, T.M. In Liposomes: the therapy of infectious diseases and cancer. Lopez-Berestein, G.; Fidler, I., Eds.; Alan R. Liss: New York, 1989, pp. 405-445.
36. Lasic, D.D.; Martin, F.J.; Gabizon, A.; Huang, S.K.; Papahadjopoulos, D. Sterically stabilized liposomes: a hypothesis on the molecular origin of the extended circulation times. Biochim. Biophys. Acta, 1991, 1070(1), 187-192.
37. Allen, T.M.; Hansen, C.; Martin, F.; Redemann, C.; Yau-Young, A. Liposomes containing synthetic lipid derivatives of poly(ethylene glycol) show prolonged circulation half-lives in vivo. Biochim. Biophys. Acta, 1991, 1066(1), 29-36.
38. Klibanov, A.L.; Maruyama, K.; Torchilin, V.P.; Huang, L. Amphipathic polyethyleneglycols effectively prolong the circulation time of liposomes. FEBS Lett., 1990, 268(1), 235-237.
39. Sou, K.; Endo, T.; Takeoka, S.; Tsuchida, E. Poly(ethylene glycol)-modification of the phospholipid vesicles by using the spontaneous incorporation of poly(ethylene glycol)-lipid into the vesicles. Bioconjug. Chem., 2000, 11(3), 372-379.
40. Uster, P.S.; Allen, T.M.; Daniel, B.E.; Mendez, C.J.; Newman, M.S.; Zhu, G.Z. Insertion of poly(ethylene glycol) derivatized phospholipid into pre-formed liposomes results in prolonged in vivo circulation time. FEBS Lett., 1996, 386(2-3), 243-246.
41. Bradley, A.J.; Devine, D.V.; Ansell, S.M.; Janzen, J.; Brooks, D.E. Inhibition of liposome-induced complement activation by incorporated poly(ethylene glycol)-lipids. Arch. Biochem. Biophys., 1998, 357(2), 185-194.
42. Vertut-Doi, A.; Ishiwata, H.; Miyajima, K. Binding and uptake of liposomes containing a poly(ethylene glycol) derivative of cholesterol(stealth liposomes) by the macrophage cell line J774: influence of PEG content and its molecular weight. Biochim. Biophys. Acta, 1996, 1278(1), 19-28.
43. Webb, M.S.; Saxon, D.; Wong, F.M.; Lim, H.J.; Wang, Z.; Bally, M.B.; Choi, L.S.; Cullis, P.R.; Mayer, L.D. Comparison of different hydrophobic anchors conjugated to poly(ethylene glycol): effects on the pharmacokinetics of liposomal vincristine. Biochim. Biophys. Acta, 1998, 1372(2), 272-282.
44. Woodle, M.C.; Lasic, D.D. Sterically stabilized liposomes. Biochim. Biophys. Acta, 1992, 1113(2), 171-199.
45. Parr, M.J.; Ansell, S.M.; Choi, L.S.; Cullis, P.R. Factors influencing the retention and chemical stability of poly(ethylene glycol)-lipid conjugates incorporated into large unilamellar vesicles. Biochim. Biophys. Acta, 1994, 1195(1), 21-30.
46. Bailey, F.E.; Koleske, J.V. In Alkylene oxides and their polymers. Marcel Dekker: New York 1991.
47. Tirosh, O.; Barenholz, Y.; Katzhendler, J.; Priev, A. Hydration of polyethylene glycol-grafted liposomes. Biophys. J., 1998, 74(3), 1371-1379.
48. Torchilin, V.P.; Omelyanenko, V.G.; Papisov, M.I.; Bogdanov, A.A.; Trubetskoy, V.S.; Herron, J.N.; Gentry, C.A. Poly(ethylene glycol) on the liposome surface: on the mechanism of polymer-coated liposome longevity. Biochim. Biophys. Acta, 1994, 1195(1), 11-20.
49. Torchilin, V.P.; Papisov, M.I. Why do polyethylene glycol-coated liposomes circulate so long? J. Liposome Res., 1994, 4(1), 725-739.
50. Kenworthy, A.K.; Hristova, K.; Needham, D.; McIntosh, T.J. Range and magnitude of the steric pressure between bilayers containing phospholipids with covalently attached polyethylene glycol. Biophys. J., 1995, 68(5), 1921-1936.
51. Kuhl, T.L.; Leckband, D.E.; Lasic, D.D.; Israelachvili, J.N. Modulation of interaction forces between bilayers exposing short-chained ethylene oxide headgroups. Biophys. J., 1994, 66(5), 1479-1488.
52. Needham, D.; McIntosh, T.J.; Lasic, D.D. Repulsive interactions and mechanical stability of polymer-grafted lipid membranes. Biochim. Biophys. Acta, 1992, 1108(1), 40-48.
53. Laverman, P.; Boerman, O.C.; Oyen, W.J.G.; Corstens, F.H.M.; Storm, G. In vivo applications of PEG liposomes: unexpected observations. Crit. Rev. Ther. Drug Carrier Syst., 2001, 18(6), 551-566.
54. Bandak, S.; Goren, D.; Horowitz, A.; Tzemach, D.; Gabizon, A. Pharmacological studies of cisplatin encapsulated in long-circulating liposomes in mouse tumor models. Anticancer Drugs, 1999, 10(10), 911-920.
55. Harrington, K.J.; Lewanski, C.R.; Northcote, A.D.; Whittaker, J.; Wellbank, H.; Vile, R.G.; Peters, A.M.; Stewart, J.S. Phase I-II study of pegylated liposomal cisplatin(SPI-077) in patients with in-operable head and neck cancer. Ann. Oncol., 2001, 12(4), 493-496.
56. Andresen, T.L.; Jensen, S.S.; Jorgensen, K. Advanced strategies in liposomal cancer therapy: problems and prospects of active and tumor specific drug release. Prog. Lipid. Res., 2005, 44(1), 68-97.
57. Needham, D.; Dewhirst, M.W. The development and testing of a new temperature-sensitive drug delivery system for the treatment of solid tumors. Adv. Drug Deliv. Rev., 2001, 53(3), 285-305.
58. Shum, P.; Kim, J.M.; Thompson, D.H. Phototriggering of liposomal drug delivery systems. Adv. Drug Deliv. Rev., 2001, 53(3), 273-284.
59. Bikram, M.; West, J.L. Thermo-responsive systems for controlled drug delivery. Expert. Opin. Drug. Deliv., 2008, 5(10), 1077-1091.
60. Schroeder, A.; Avnir, Y.; Weisman, S.; Najajreh, Y.; Gabizon, A.; Talmon, Y.; Kost, J.; Barenholz, Y. Controlling liposomal drug release with low frequency ultrasound: mechanism and feasibility. Langmuir, 2007, 23(7), 4019-4025.
61. Meers, P. Enzyme-activated targeting of liposomes. Adv. Drug Deliv. Rev., 2001, 53(3), 265-272.
62. Drummond, D.C.; Zignani, M.; Leroux, J. Current status of pH-sensitive liposomes in drug delivery. Prog. Lipid Res., 2000, 39(5), 409-460.
63. Karanth, H.; Murthy, R.S. pH-sensitive liposomes - principle and application in cancer therapy. J. Pharm. Pharmacol., 2007, 59(4), 469-483.
64. Torchilin, V. Multifunctional and stimuli-sensitive pharmaceutical nanocarriers. Eur. J. Pharm. Biopharm., 2009, 71(3), 431-444.
65. Yatvin, M.B.; Weinstein, J.N.; Dennis, W.H.; Blumenthal, R. Design of liposomes for enhanced local release of drugs by hyperthermia. Science, 1978, 202(4374), 1290-1293.
66. Weinstein, J.N.; Magin, R.L.; Yatvin, M.B.; Zaharko, D.S. Liposomes and local hyperthermia: selective delivery of methotrexate to heated tumors. Science, 1979, 204(4389), 188-191.
67. Anyarambhatla, G.R.; Needham, D. Enhancement of the phase transition permeability of DPPC liposomes by incorporation of MPPC: a new temperature-sensitive liposome for use with mild hyperthermia. J. Lipsome Res., 1999, 9, 491-506.
68. Kong, G.; Anyarambhatla, G.; Petros, W.P.; Braun, R.D.; Colvin, O.M.; Needham, D.; Dewhirst, M.W. Efficacy of liposomes and hyperthermia in a human tumor xenograft model: importance of triggered drug release. Cancer Res., 2000, 60(24), 6950-6957.
69. Needham, D.; Anyarambhatla, G.; Kong, G.; Dewhirst, M.W. A new temperature-sensitive liposome for use with mild hyperthermia: characterization and testing in a human tumor xenograft model. Cancer Res., 2000, 60(5), 1197-1201.
70. Available from: U.S. National Institutes of Health. National Library of Medicine. http://www.clinialtrials.gov.
71. Sapra, P.; Tyagi, P.; Allen, T.M. Ligand-targeted liposomes for cancer treatment. Curr. Drug Deliv., 2005, 2(4), 369-381.
72. Allen, T.M. Ligand-targeted therapeutics in anticancer therapy. Nat. Rev. Cancer, 2002, 2(10), 750-763.
73. Torchilin, V. Antibody-modified liposomes for cancer chemotherapy. Expert Opin. Drug Deliv., 2008, 5(9), 1003-1025.
74. Noble, C.O.; Kirpotin, D.B.; Hayes, M.E.; Mamot, C.; Hong, K.; Park, J.W.; Benz, C.C.; Marks, J.D.; Drummond, D.C. Development of ligand-targeted liposomes for cancer therapy. Expert Opin. Ther. Targets, 2004, 8(4), 335-353.
75. Jain, R.K. Barriers to drug delivery in solid tumors. Sci. Am., 1994, 271(1), 58-65.
76. Jain, R.K.; Baxter, L.T. Mechanisms of heterogeneous distribution of monoclonal antibodies and other macromolecules in tumors: significance of elevated interstitial pressure. Cancer Res., 1988, 48(24 Pt 1), 7022-7032.
77. Lopes de Menezes, D.E.; Pilarski, L.M.; Allen, T.M. In vitro and in vivo targeting of immunoliposomal doxorubicin to human B-cell lymphoma. Cancer Res., 1998, 58(15), 3320-3330.
78. Allen, T.M.; Mumbengegwi, D.R.; Charrois, G.J. Anti-CD19-targeted liposomal doxorubicin improves the therapeutic efficacy in murine B-cell lymphoma and ameliorates the toxicity of liposomes with varying drug release rates. Clin. Cancer Res., 2005, 11(9), 3567-3573.
79. Park, J.W.; Hong, K.; Kirpotin, D.B.; Colbern, G.; Shalaby, R.; Baselga, J.; Shao, Y.; Nielsen, U.B.; Marks, J.D.; Moore, D.; Papahadjopoulos, D.; Benz, C.C. Anti-HER2 immunoliposomes: enhanced efficacy attributable to targeted delivery. Clin. Cancer Res., 2002, 8(4), 1172-1181.
80. Park, J.W.; Hong, K.; Carter, P.; Asgari, H.; Guo, L.Y.; Keller, G.A.; Wirth, C.; Shalaby, R.; Kotts, C.; Wood, W.I.; Papahadjopoulos, D.; Benz, C.C. Development of anti-p185HER2 immunoliposomes for cancer therapy. Proc. Natl. Acad. Sci. USA, 1995, 92(5), 1327-1331.
81. Nellis, D.F.; Ekstrom, D.L.; Kirpotin, D.B.; Zhu, J.; Andersson, R.; Broadt, T.L.; Ouellette, T.F.; Perkins, S.C.; Roach, J.M.; Drummond, D.C.; Hong, K.; Marks, J.D.; Park, J.W.; Giardina, S.L. Pre-clinical manufacture of an anti-HER2 scFv-PEG-DSPE, liposome-inserting conjugate. 1. Gram-scale production and purification. Biotechnol. Prog., 2005, 21(1)., 205-220.
82. Nellis, D.F.; Giardina, S.L.; Janini, G.M.; Shenoy, S.R.; Marks, J.D.; Tsai, R.; Drummond, D.C.; Hong, K.; Park, J.W.; Ouellette, T.F.; Perkins, S.C.; Kirpotin, D.B. Preclinical manufacture of anti-HER2 liposome-inserting, scFv-PEG-lipid conjugate. 2. Conjugate micelle identity, purity, stability, and potency analysis. Biotechnol. Prog., 2005, 21(1), 221-232.
83. Mayer, L.D.; Bally, M.B.; Cullis, P.R. Uptake of adriamycin into large unilamellar vesicles in response to a pH gradient. Biochim. Biophys. Acta., 1986, 857(1), 123-126.
84. Mayer, L.D.; Bally, M.B.; Hope, M.J.; Cullis, P.R. Uptake of anti-neoplastic agents into large unilamellar vesicles in response to a membrane potential. Biochim. Biophys. Acta, 1985, 816(2), 294-302.
85. Abraham, S.A.; Waterhouse, D.N.; Mayer, L.D.; Cullis, P.R.; Madden, T.D.; Bally, M.B. The liposomal formulation of doxorubicin. Methods Enzymol., 2005, 391, 71-97.
86. Tardi, P.; Choice, E.; Masin, D.; Redelmeier, T.; Bally, M.; Madden, T.D. Liposomal encapsulation of topotecan enhances anticancer efficacy in murine and human xenograft models. Cancer Res., 2000, 60(13), 3389-3393.
87. Fenske, D.B.; Wong, K.F.; Maurer, E.; Maurer, N.; Leenhouts, J.M.; Boman, N.; Amankwa, L.; Cullis, P.R. Ionophore-mediated uptake of ciprofloxacin and vincristine into large unilamellar vesicles exhibiting transmembrane ion gradients. Biochim. Biophys. Acta., 1998, 1414(1-2), 188-204.
88. Li, X.; Hirsh, D.J.; Cabral-Lilly, D.; Zirkel, A.; Gruner, S.M.; Janoff, A.S.; Perkins, W.R. Doxorubicin physical state in solution and inside liposomes loaded via a pH gradient. Biochim. Biophys. Acta, 1998, 1415(1), 23-40.
89. Lasic, D.D.; Frederik, P.M.; Stuart, M.C.; Barenholz, Y.; McIntosh, T.J. Gelation of liposome interior. A novel method for drug encapsulation. FEBS Lett., 1992, 312(2-3), 255-258.
90. Abraham, S.A.; Edwards, K.; Karlsson, G.; MacIntosh, S.; Mayer, L.D.; McKenzie, C.; Bally, M.B. Formation of transition metal-doxorubicin complexes inside liposomes. Biochim. Biophys. Acta, 2002, 1565(1), 41-54.
91. Taggar, A.S.; Alnajim, J.; Anantha, M.; Thomas, A.; Webb, M.; Ramsay, E.; Bally, M.B. Copper-topotecan complexation mediates drug accumulation into liposomes. J. Control Release, 2006, 114(1), 78-88.
92. Ramsay, E.; Alnajim, J.; Anantha, M.; Taggar, A.; Thomas, A.; Edwards, K.; Karlsson, G.; Webb, M.; Bally, M. Transition metal-mediated liposomal encapsulation of irinotecan(CPT-11) stabilizes the drug in the therapeutically active lactone conformation. Pharm. Res., 2006, 23(12), 2799-2808.
93. Berenbaum, M.C. Synergy, additivism and antagonism in immunosuppression. A critical review. Clin. Exp. Immunol., 1977, 28(1), 1-18.
94. Berenbaum, M.C. What is synergy? Pharmacol. Rev., 1989, 41(2), 93-141.
95. Chou, T.C. Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol. Rev., 2006, 58(3), 621-681.
96. Greco, W.R.; Bravo, G.; Parsons, J.C. The search for synergy: a critical review from a response surface perspective. Pharmacol. Rev., 1995, 47(2), 331-385.
97. Mayer, L.D.; Janoff, A.S. Optimizing combination chemotherapy by controlling drug ratios. Mol. Interv., 2007, 7(4), 216-223.
98. U.S. Food and Drug Administration. Combination Products. Available from: http://www.fda.gov/combinationproducts/default.htm [accessed December 9, 2009].
99. Abraham, S.A.; McKenzie, C.; Masin, D.; Ng, R.; Harasym, T.O.; Mayer, L.D.; Bally, M.B. In vitro and in vivo characterization of doxorubicin and vincristine coencapsulated within liposomes through use of transition metal ion complexation and pH gradient loading. Clin. Cancer Res., 2004, 10(2), 728-738.
100. Batist, G.; Gelmon, K.A.; Chi, K.N.; Miller, W.H., Jr.; Chia, S.K.; Mayer, L.D.; Swenson, C.E.; Janoff, A.S.; Louie, A.C. Safety, pharmacokinetics, and efficacy of CPX-1 liposome injection in patients with advanced solid tumors. Clin. Cancer Res., 2009, 15(2), 692-700.
101. Dicko, A.; Frazier, A.A.; Liboiron, B.D.; Hinderliter, A.; Ellena, J.F.; Xie, X.; Cho, C.; Weber, T.; Tardi, P.G.; Cabral-Lilly, D.; Cafiso, D.S.; Mayer, L.D. Intra and inter-molecular interactions dictate the aggregation state of irinotecan co-encapsulated with floxuridine inside liposomes. Pharm. Res., 2008, 25(7), 1702-1713.
102. Harasym, T.O.; Tardi, P.G.; Harasym, N.L.; Harvie, P.; Johnstone, S.A.; Mayer, L.D. Increased preclinical efficacy of irinotecan and floxuridine coencapsulated inside liposomes is associated with tumor delivery of synergistic drug ratios. Oncol. Res., 2007, 16(8), 361-374.
103. Tardi, P.G.; Gallagher, R.C.; Johnstone, S.; Harasym, N.; Webb, M.; Bally, M.B.; Mayer, L.D. Coencapsulation of irinotecan and floxuridine into low cholesterol-containing liposomes that coordinate drug release in vivo. Biochim. Biophys. Acta, 2007, 1768(3), 678-687.
104. Bayne, W.F.; Mayer, L.D.; Swenson, C.E. Pharmacokinetics of CPX-351(cytarabine/daunorubicin HCl) liposome injection in the mouse. J. Pharm. Sci., 2009, 98(7), 2540-2548.
105. Tardi, P.; Johnstone, S.; Harasym, N.; Xie, S.; Harasym, T.; Zisman, N.; Harvie, P.; Bermudes, D.; Mayer, L. In vivo maintenance of synergistic cytarabine:daunorubicin ratios greatly enhances therapeutic efficacy. Leuk. Res., 2009, 33(1), 129-139.
106. Zhao, X.; Wu, J.; Muthusamy, N.; Byrd, J.C.; Lee, R.J. Liposomal coencapsulated fludarabine and mitoxantrone for lymphoproliferative disorder treatment. J. Pharm. Sci., 2008, 97(4), 1508-1518.
107. Gottesman, M.M. How cancer cells evade chemotherapy: sixteenth Richard and Hinda Rosenthal Foundation Award Lecture. Cancer Res., 1993, 53(4), 747-754.
108. Gottesman, M.M.; Fojo, T.; Bates, S.E. Multidrug resistance in cancer: role of ATP-dependent transporters. Nat. Rev. Cancer, 2002, 2(1), 48-58.
109. El-Deiry, W.S. The role of p53 in chemosensitivity and radiosensitivity. Oncogene, 2003, 22(47), 7486-7495.
110. Pommier, Y.; Sordet, O.; Antony, S.; Hayward, R.L.; Kohn, K.W. Apoptosis defects and chemotherapy resistance: molecular interaction maps and networks. Oncogene, 2004, 23(16), 2934-2949.
111. Jain, R.K. Therapeutic implications of tumor physiology. Curr. Opin. Oncol., 1991, 3(6), 1105-1108.
112. Juliano, R.L.; Ling, V. A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim. Biophys. Acta, 1976, 455(1), 152-162.
113. Suzuki, T.; Nishio, K.; Tanabe, S. The MRP family and anticancer drug metabolism. Curr. Drug Metab., 2001, 2(4), 367-377.
114. Ahmed-Belkacem, A.; Pozza, A.; Macalou, S.; Perez-Victoria, J.M.; Boumendjel, A.; Di Pietro, A. Inhibitors of cancer cell multidrug resistance mediated by breast cancer resistance protein(BCRP/ABCG2). Anticancer Drugs, 2006, 17(3), 239-243.
115. Scheffer, G.L.; Schroeijers, A.B.; Izquierdo, M.A.; Wiemer, E.A.; Scheper, R.J. Lung resistance-related protein/major vault protein and vaults in multidrug-resistant cancer. Curr. Opin. Oncol., 2000, 12(6), 550-556.
116. Perez-Tomas, R. Multidrug resistance: retrospect and prospects in anti-cancer drug treatment. Curr. Med. Chem., 2006, 13(16), 1859-1876.
117. Krishna, R.; Mayer, L.D. The use of liposomal anticancer agents to determine the roles of drug pharmacodistribution and P-glycoprotein(PGP) blockade in overcoming multidrug resistance(MDR). Anticancer Res., 1999, 19(4B), 2885-2891.
118. Advani, R.; Fisher, G.A.; Lum, B.L.; Hausdorff, J.; Halsey, J.; Litchman, M.; Sikic, B.I. A phase I Trial of doxorubicin, paclitaxel, and valspodar(PSC 833), a modulator of multidrug resistance. Clin. Cancer Res., 2001, 7(5), 1221-1229.
119. Fracasso, P.M.; Brady, M.F.; Moore, D.H.; Walker, J.L.; Rose, P.G.; Letvak, L.; Grogan, T.M.; McGuire, W.P. Phase II Study of Paclitaxel and Valspodar(PSC 833) in Refractory Ovarian Carcinoma: A Gynecologic Oncology Group Study. J. Clin. Oncol., 2001, 19(12), 2975-2982.
120. Friedenberg, W.R.; Rue, M.; Blood, E.A.; Dalton, W.S.; Shustik, C.; Larson, R.A.; Sonneveld, P.; Greipp, P.R. Phase III study of PSC-833(valspodar) in combination with vincristine, doxorubicin, and dexamethasone(valspodar/VAD) versus VAD alone in patients with recurring or refractory multiple myeloma(E1A95): a trial of the Eastern Cooperative Oncology Group. Cancer, 2006, 106(4), 830-838.
121. Wang, J.; Goh, B.; Lu, W.; Zhang, Q.; Chang, A.; Liu, X.Y.; Tan, T.M.C.; Lee, H. In Vitro Cytotoxicity of Stealth Liposomes Co-encapsulating Doxorubicin and Verapamil on Doxorubicin-Resistant Tumor Cells. Biolog. Pharma. Bull., 2005, 28(5), 822-828.
122. Wang, J.C.; Liu, X.Y.; Lu, W.L.; Chang, A.; Zhang, Q.; Goh, B.C.; Lee, H.S. Pharmacokinetics of intravenously administered stealth liposomal doxorubicin modulated with verapamil in rats. Eur. J. Pharm. Biopharm., 2006, 62(1), 44-51.
123. Wu, J.; Lu, Y.; Lee, A.; Pan, X.; Yang, X.; Zhao, X.; Lee, R.J. Reversal of multidrug resistance by transferrin-conjugated liposomes co-encapsulating doxorubicin and verapamil. J. Pharm. Pharm. Sci., 2007, 10(3), 350-357.
124. Gottesman, M.M.; Pastan, I.; Ambudkar, S.V. P-glycoprotein and multidrug resistance. Curr. Opin. Genet. Dev., 1996, 6(5), 610-617.
125. Li, X.; Lu, W.L.; Liang, G.W.; Ruan, G.R.; Hong, H.Y.; Long, C.; Zhang, Y.T.; Liu, Y.; Wang, J.C.; Zhang, X.; Zhang, Q. Effect of stealthy liposomal topotecan plus amlodipine on the multidrug-resistant leukaemia cells in vitro and xenograft in mice. Eur. J. Clin. Invest., 2006, 36(6), 409-418.
126. Liang, G.W.; Lu, W.L.; Wu, J.W.; Zhao, J.H.; Hong, H.Y.; Long, C.; Li, T.; Zhang, Y.T.; Zhang, H.; Wang, J.C.; Zhang, X.; Zhang, Q. Enhanced therapeutic effects on the multi-drug resistant human leukemia cells in vitro and xenograft in mice using the stealthy liposomal vincristine plus quinacrine. Fundam. Clin. Pharmacol., 2008, 22(4), 429-437.
127. Rosa, D.D.; Ismael, G.; Lago, L.D.; Awada, A. Molecular-targeted therapies: lessons from years of clinical development. Cancer Treat. Rev., 2008, 34(1), 61-80.
128. Cartron, G.; Watier, H.; Golay, J.; Solal-Celigny, P. From the bench to the bedside: ways to improve rituximab efficacy. Blood, 2004, 104(9), 2635-2642.
129. Harris, M. Monoclonal antibodies as therapeutic agents for cancer. Lancet Oncol., 2004, 5(5), 292-302.
130. von Mehren, M.; Adams, G.P.; Weiner, L.M. Monoclonal antibody therapy for cancer. Annu. Rev. Med., 2003, 54, 343-369.
131. de Fougerolles, A.; Vornlocher, H.P.; Maraganore, J.; Lieberman, J. Interfering with disease: a progress report on siRNA-based therapeutics. Nat. Rev. Drug Discov., 2007, 6(6), 443-453.
132. Mahato, R.I.; Cheng, K.; Guntaka, R.V. Modulation of gene expression by antisense and antigene oligodeoxynucleotides and small interfering RNA. Expert Opin. Drug Deliv., 2005, 2(1), 3-28.
133. Edelstein, M.L.; Abedi, M.R.; Wixon, J.; Edelstein, R.M. Gene therapy clinical trials worldwide 1989-2004-an overview. J. Gene Med., 2004, 6(6), 597-602.
134. Bartsch, M.; Weeke-Klimp, A.H.; Meijer, D.K.; Scherphof, G.L.; Kamps, J.A. Cell-specific targeting of lipid-based carriers for ODN and DNA. J. Liposome Res., 2005, 15(1-2), 59-92.
135. de Fougerolles, A.R. Delivery vehicles for small interfering RNA in vivo. Hum. Gene Ther., 2008, 19(2), 125-132.
136. Castanotto, D.; Rossi, J.J. The promises and pitfalls of RNA-interference-based therapeutics. Nature, 2009, 457(7228), 426-433.
137. Whitehead, K.A.; Langer, R.; Anderson, D.G. Knocking down barriers: advances in siRNA delivery. Nat. Rev. Drug Discov., 2009, 8(2), 129-138.
138. Dimitriadis, G.J. Entrapment of plasmid DNA in liposomes. Nucleic. Acids. Res., 1979, 6(8), 2697-2705.
139. Mukherjee, A.B.; Orloff, S.; Butler, J.D.; Triche, T.; Lalley, P.; Schulman, J.D. Entrapment of metaphase chromosomes into phospholipid vesicles(lipochromosomes): carrier potential in gene transfer. Proc. Natl. Acad. Sci. USA, 1978, 75(3), 1361-1365.
140. Wreschner, D.H.; Gregoriadis, G.; Gunner, D.B.; Dourmashkin, R.R. Entrapment of mRNA and rRNA into large monolamellar liposomes derived from hybrid small monolamellar liposomes. Biochem. Soc. Trans., 1978, 6(5), 930-933.
141. Felgner, P.L.; Gadek, T.R.; Holm, M.; Roman, R.; Chan, H.W.; Wenz, M.; Northrop, J.P.; Ringold, G.M.; Danielsen, M. Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure. Proc. Natl. Acad. Sci. USA, 1987, 84(21), 7413-7417.
142. Felgner, P.L.; Ringold, G.M. Cationic liposome-mediated transfection. Nature, 1989, 337(6205), 387-388.
143. Rait, A.S.; Pirollo, K.F.; Ulick, D.; Cullen, K.; Chang, E.H. HER-2-targeted antisense oligonucleotide results in sensitization of head and neck cancer cells to chemotherapeutic agents. Ann. N.Y. Acad. Sci., 2003, 1002, 78-89.
144. Rait, A.S.; Pirollo, K.F.; Xiang, L.; Ulick, D.; Chang, E.H. Tumor-targeting, systemically delivered antisense HER-2 chemosensitizes human breast cancer xenografts irrespective of HER-2 levels. Mol. Med., 2002, 8(8), 475-486.
145. Wang, Y.; Pakunlu, R.I.; Tsao, W.; Pozharov, V.; Minko, T. Bimodal effect of hypoxia in cancer: role of hypoxia inducible factor in apoptosis. Mol. Pharm., 2004, 1(2), 156-165.
146. Wang, Y.; Saad, M.; Pakunlu, R.I.; Khandare, J.J.; Garbuzenko, O.B.; Vetcher, A.A.; Soldatenkov, V.A.; Pozharov, V.P.; Minko, T. Nonviral nanoscale-based delivery of antisense oligonucleotides targeted to hypoxia-inducible factor 1 alpha enhances the efficacy of chemotherapy in drug-resistant tumor. Clin. Cancer Res., 2008, 14(11), 3607-3616.
147. Pakunlu, R.I.; Cook, T.J.; Minko, T. Simultaneous modulation of multidrug resistance and antiapoptotic cellular defense by MDR1 and BCL-2 targeted antisense oligonucleotides enhances the anticancer efficacy of doxorubicin. Pharm. Res., 2003, 20(3), 351-359.
148. Saad, M.; Garbuzenko, O.B.; Minko, T. Co-delivery of siRNA and an anticancer drug for treatment of multidrug-resistant cancer. Nanomedicine, 2008, 3(6), 761-776.
149. Ko, Y.T.; Falcao, C.; Torchilin, V.P. Cationic liposomes loaded with proapoptotic peptide D-(KLAKLAK)(2) and Bcl-2 antisense oligodeoxynucleotide G3139 for enhanced anticancer therapy. Mol. Pharm., 2009, 6(3), 971-977.
150. Li, S.D.; Chono, S.; Huang, L. Efficient oncogene silencing and metastasis inhibition via systemic delivery of siRNA. Mol. Ther., 2008, 16(5), 942-946.
151. Judge, A.D.; Sood, V.; Shaw, J.R.; Fang, D.; McClintock, K.; MacLachlan, I. Sequence-dependent stimulation of the mammalian innate immune response by synthetic siRNA. Nat. Biotechnol., 2005, 23(4), 457-462.
152. Robbins, M.; Judge, A.; MacLachlan, I. siRNA and innate immunity. Oligonucleotides, 2009, 19(2), 89-102.
153. Garg, A.K.; Buchholz, T.A.; Aggarwal, B.B. Chemosensitization and radiosensitization of tumors by plant polyphenols. Antioxid. Redox. Signal., 2005, 7(11-12), 1630-1647.
154. Shah, M.A.; Schwartz, G.K. Cell cycle-mediated drug resistance: an emerging concept in cancer therapy. Clin. Cancer Res., 2001, 7(8), 2168-2181.
155. Conklin, K.A. Dietary antioxidants during cancer chemotherapy: impact on chemotherapeutic effectiveness and development of side effects. Nutr. Cancer, 2000, 37(1), 1-18.
156. Chowdhury, S.A.; Kishino, K.; Satoh, R.; Hashimoto, K.; Kikuchi, H.; Nishikawa, H.; Shirataki, Y.; Sakagami, H. Tumor-specificity and apoptosis-inducing activity of stilbenes and flavonoids. Anticancer Res., 2005, 25(3B)., 2055-2063.
157. Matsuo, M.; Sasaki, N.; Saga, K.; Kaneko, T. Cytotoxicity of flavonoids toward cultured normal human cells. Biol. Pharm. Bull., 2005, 28(2), 253-259.
158. Goniotaki, M.; Hatziantoniou, S.; Dimas, K.; Wagner, M.; Demetzos, C. Encapsulation of naturally occurring flavonoids into liposomes: physicochemical properties and biological activity against human cancer cell lines. J. Pharm. Pharmacol., 2004, 56(10), 1217-1224.
159. Liu, Y.; Lu, W.L.; Guo, J.; Du, J.; Li, T.; Wu, J.W.; Wang, G.L.; Wang, J.C.; Zhang, X.; Zhang, Q. A potential target associated with both cancer and cancer stem cells: a combination therapy for eradication of breast cancer using vinorelbine stealthy liposomes plus parthenolide stealthy liposomes. J. Control. Release, 2008, 129(1), 18-25.
160. Ogretmen, B.; Hannun, Y.A. Biologically active sphingolipids in cancer pathogenesis and treatment. Nat. Rev. Cancer, 2004, 4(8), 604-616.
161. Ogretmen, B. Sphingolipids in cancer: Regulation of pathogenesis and therapy. FEBS Lett., 2006, 580(23), 5467-5476.
162. Perkins, W.R.; Dause, R.B.; Li, X.; Franklin, J.C.; Cabral-Lilly, D.J.; Zha, Y.; Dank, E.H.; Mayhew, E.; Janoff, A.S. Combination of antitumor ether lipid with lipids of complementary molecular shape reduces its hemolytic activity. Biochim. Biophys. Acta, 1997, 1327(1), 61-68.
163. Bhamra, R.; Bolcsak, L.E.; Roberts, P.; Stevens, R.; Cavanaugh, C.; Swenson, C.E. Toxicity and disposition of TLC ELL-12(liposomal antitumor ether lipid) in Sprague-Dawley rats. Anticancer Drugs, 2003, 14(3), 183-191.
164. Zeisig, R.; Fichtner, I.; Arndt, D.; Jungmann, S. Antitumor effects of alkylphosphocholines in different murine tumor models: use of liposomal preparations. Anti-cancer Drugs, 1991, 2(4), 411-417.
165. Stover, T.C.; Sharma, A.; Robertson, G.P.; Kester, M. Systemic delivery of liposomal short-chain ceramide limits solid tumor growth in murine models of breast adenocarcinoma. Clin. Cancer Res., 2005, 11(9), 3465-3474.
166. Shabbits, J.A.; Mayer, L.D. High ceramide content liposomes with in vivo antitumor activity. Anticancer Res., 2003, 23(5A), 3663-3669.
167. Unger, C.; Eibl, H.; Breiser, A.; von Heyden, H.W.; Engel, J.; Hilgard, P.; Sindermann, H.; Peukert, M.; Nagel, G.A. Hexadecylphosphocholine(D 18506) in the topical treatment of skin metastases: a phase-I trial. Onkologie, 1988, 11(6), 295-296.
168. Kaufmann-Kolle, P.; Drevs, J.; Berger, M.R.; Kotting, J.; Marschner, N.; Unger, C.; Eibl, H. Pharmacokinetic behavior and antineoplastic activity of liposomal hexadecylphosphocholine. Cancer Chemother. Pharmacol., 1994, 34(5), 393-398.
169. Wilson, H.M.; Neumuller, W.; Eibl, H.; Welch, W.H., Jr.; Reitz, R.C. Structural basis of the phospholipid acyltransferase enzyme substrate specificity: a computer modeling study of the phospholipid acceptor molecule. J. Lipid Res., 1995, 36(3), 429-439.
170. Arndt, D.; Zeisig, R.; Bechtel, D.; Fichtner, I. Liposomal bleomycin: increased therapeutic activity and decreased pulmonary toxicity in mice. Drug. Deliv., 2001, 8(1), 1-7.
171. Papagiannaros, A.; Hatziantoniou, S.; Dimas, K.; Papaioannou, G.T.; Demetzos, C. A liposomal formulation of doxorubicin, composed of hexadecylphosphocholine(HePC): physicochemical characterization and cytotoxic activity against human cancer cell lines. Biomed. Pharmacother., 2006, 60(1), 36-42.
172. Papagiannaros, A.; Hatziantoniou, S.; Lelong-Rebel, I.H.; Papaioannou, G.T.; Dimas, K.; Demetzos, C. Antitumor activity of doxorubicin encapsulated in hexadecylphosphocholine(HePC) liposomes against human xenografts on Scid mice. In Vivo, 2006., 20(1), 129-135.
173. Lundberg, B.B. Ether lipids enhance the cytotoxic effect of teniposide and paclitaxel in liposomes against leukaemic cells in culture. Anti-Cancer Drug Design, 1997, 12(6), 503-513.
174. Harashima, H.; Iida, S.; Urakami, Y.; Tsuchihashi, M.; Kiwada, H. Optimization of antitumor effect of liposomally encapsulated doxorubicin based on simulations by pharmacokinetic/ pharmacodynamic modeling. J. Control. Release, 1999, 61(1-2), 93-106.
175. Harashima, H.; Tsuchihashi, M.; Iida, S.; Doi, H.; Kiwada, H. Pharmacokinetic/pharmacodynamic modeling of antitumor agents encapsulated into liposomes. Adv. Drug Deliv. Rev., 1999, 40(1-2), 39-61.