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Liposomal Drug Delivery Systems for Cancer Therapy

  • Chapter
Drug Delivery Systems in Cancer Therapy

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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Abstract

Liposomes are currently one of the most well-studied drug delivery systems used in the treatment of cancer. They are being employed in the treatment of a wide variety of human malignancies (1–4). Their large size relative to the gaps in the vasculature of healthy tissues inhibits their uptake by these tissues, thus avoiding certain nonspecific toxicities. However, the “leaky” microvasculature supporting solid tumors allows for the uptake of these large (~ 100 nm) drug carriers (5–8) and their subsequent interaction with cancer cells (9), or release of the encapsulated drug specifically near the tumor, where it can diffuse into the tumor in its free form (10,11). Liposomes have many other potential advantages over the corresponding free drugs, including favorable pharmacokinetic properties, where encapsulation of a usually rapidly cleared drug results in a considerable increase in the circulation lifetime for the drug (12–14). In addition, encapsulation or complexation of a normally labile therapeutic agent, such as DNA, antisense oligonucleotides, or the lactone ring of camptothecins, can protect the agent from premature degradation by enzymes in the plasma or from simple hydrolysis. The result of liposome formulation can thus be a substantial increase in antitumor efficacy when compared to the free drug or standard chemotherapy regimens (15–17).

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References

  1. Gabizon AA. Clinical trials of liposomes as carriers of chemotherapeutic agents: synopsis and perspective, in Medical Applications of Liposomes (Lasic DD, Papahadjopoulos D, eds). Elsevier Science B.V., New York, 1998, pp 625–634.

    Chapter  Google Scholar 

  2. Martin FJ. Clinical pharmacology and antitumor efficacy ot DUXIL (pegyiated liposomal doxorubicin), in Medical Applications of Liposomes (Lasic DD, Papahadjopoulos D, eds). Elsevier Science B.V., New York, 1998, pp 635–688.

    Chapter  Google Scholar 

  3. Drummond DC, Meyer OM, Hong K, Kirpotin DB, Papahadjopoulos D. Optimizing liposomes for delivery of chemotherapeutic agents to solid tumors. Pharmacol Rev 1999;51:691–743.

    PubMed  CAS  Google Scholar 

  4. Gelmon KA, Tolcher A, Diab AR, et al. Phase I study of liposomal vincristine. Uncot 1999; 17:697–705.

    CAS  Google Scholar 

  5. Hobbs SK, Monsky WL, Yuan F, et al. Regulation ot transport pathways in tumor vessels: role or tumor type and microenvironment. Proc Natl Acad Sci USA 1998; 95:4607–4612.

    Article  PubMed  CAS  Google Scholar 

  6. Huang SK, Martin FJ, Jay G, Vogel J, Papahadjopoulos D, Friend DS. Extravasation and transcytosis of liposomes in Kaposi’s sarcoma-like dermal lesions of transgenic mice bearing the HIV Tat gene. Am J Path 1993; 143:10–14.

    PubMed  CAS  Google Scholar 

  7. Yuan F, Lwunig M, Huang SK, Berk DA, Papahadjopoulos D, Jain RK. Microvascular permeability and interstitial penetration of sterically stabilized (stealth) liposomes in a human tumor xenograft. Cancer Res 1994; 54:3352–3356.

    PubMed  CAS  Google Scholar 

  8. Yuan F, Dellian M, Fukumura D, et al. Vascular permeability in a human tumor xenogratt: molecular size dependence and cutoff size. Cancer Res 1995; 55:3752–3756.

    PubMed  CAS  Google Scholar 

  9. Park JW, Hong K, Kirpotin DB, Meyer O, Papahadjopoulos D, Benz CC. Anti-HER2 immunoliposomes for targeted therapy of human tumors. Cancer Lett 1997; 118:153–160.

    Article  PubMed  CAS  Google Scholar 

  10. Horowitz AR, Barenholz Y, Gabizon AA. In vitro cytotoxicity ot liposome-encapsulatea doxorubicin: dependence on liposome composition and drug release. Biochim Biophys Acta 1992; 1109:203–209.

    Article  PubMed  CAS  Google Scholar 

  11. Vaage J, Donovan D, Working P, Uster P. Cellular distribution of DUXIL within selectee tissues, assessed by confocal laser scanning microscopy, in Medical Applications of Liposomes (Lasic D, Papahadjopoulos D, ed). Elsevier Science B.V., New York, 1998, pp 275–282.

    Chapter  Google Scholar 

  12. Hwang KJ, Liposome pharmacokinetics, in Liposomes: from biophysics to therapeutics (Ostro MJ, ed). Marcel Dekker, New York, 1987, pp 109–156.

    Google Scholar 

  13. Allen TM, Hansen CB, Lopes de Menezes DE. Pharmacokinetics of long-circulating liposomes. Adv Drug Del Rev 1995; 16:267–284.

    Article  CAS  Google Scholar 

  14. Allen TM, Stuart DD. Liposome pharmacokinetics. Classical, sterically-stabilized, cationic liposomes and immunoliposomes, in Liposomes: Rational Design (Janoff AS, ed). Marcel Dekker, New York, 1999, pp 63–87.

    Google Scholar 

  15. Gabizon A, Catane R, Uziely B, Kaufman B, Safra T. Prolonged circulation time and enhanced accumulation in malignant exudates of doxorubicin encapsulated in polyethylene-glycol coated liposomes. Cancer Res 1994; 54:987–992.

    PubMed  CAS  Google Scholar 

  16. Northfelt DW, Dezube BJ, Thommes JA, et al. Pegylated-liposomal doxorubicin versus doxorubicin, bleomycin, and vincristine in the treatment of AIDS-related Kaposi’s sarcoma: results of a randomized phase III clinical trial. J Clin Oncol 1998; 16:2445–2551.

    PubMed  CAS  Google Scholar 

  17. Stewart S, Jablonowski H, Goebel FD, et al. Randomized comparative trial of pegylated liposomal doxorubicin versus bleomycin and vincristine in the treatment of AIDS-related Kaposi’s sarcoma. J Clin Oncol 1998; 16:683–691.

    PubMed  CAS  Google Scholar 

  18. Klibanov AL, Maruyama K, Torchilin VP, Huang L. Amphipathic polyethyleneglycols effectively prolong the circulation time of liposomes. FEBS Leu 1990; 268:235–237.

    Article  CAS  Google Scholar 

  19. Papahadjopoulos D, Allen TM, Gabizon A, et al. Sterically stabilized liposomes: improvements in pharmacokinetics and antitumor therapeutic efficacy. Proc Natl Acad Sci USA 1991; 88:11460–11464.

    Article  PubMed  CAS  Google Scholar 

  20. Allen TM, Newman MS, Woodle MC, Mayhew E, Uster PS. Pharmacokinetics and anti-tumor activity of vincristine encapsulated in sterically stabilized liposomes. Int J Cancer 1995: 62:199–204

    Article  PubMed  CAS  Google Scholar 

  21. Woodle MC. Controlling liposome blood clearance by surface-grafted polymers. Adv Drug Del Rev 1998; 32:139–152.

    Article  CAS  Google Scholar 

  22. Bally MB, Lim H, Cullis PR, Mayer LD. Controlling the drug delivery attributes of lipid-based drug formulations. J Liposome Res 1998; 8:299–335.

    Article  CAS  Google Scholar 

  23. Barenholz Y. Design of liposome-based drug carriers: from basic research to application as approved drugs, in Medical Applications of Liposomes (Lasic DD, Papahadjopoulos D, eds). Elsevier Science B.V., New York, 1998, pp 545–565.

    Chapter  Google Scholar 

  24. Kirpotin DB, Park JW, Hong K, et al. Targeting of liposomes to solid tumors: the case of sterically stabilized anti-HER2 immunoliposomes. J Liposome Res 1997; 7:391–417.

    Article  CAS  Google Scholar 

  25. Park JW, Hong K, Kirpotin DB, Papahadjopoulos D, Benz CC. Immunoliposomes for cancer treatment. Adv Pharmacol 1997; 40:399–435.

    Article  PubMed  CAS  Google Scholar 

  26. Senior JH. Fate and behaviour of liposomes in vivo: a review of controlling factors. CRC Crit Rev Therap Drug Carrier System 1987; 3:123–193.

    CAS  Google Scholar 

  27. Abra RM, Hunt CA. Liposome disposition in vivo. III. Dose and vesicle-size effects. Biochim Biophys Acta 1981; 666:493–503.

    Article  PubMed  CAS  Google Scholar 

  28. Ishida O, Maruyama K, Sasaki K, Iwatsuru M. Size-dependent extravasation and interstitial localization of polyethyleneglycol liposomes in solid tumor-bearing mice. Int J Pharmaceut 1999; 190:49–56.

    Article  CAS  Google Scholar 

  29. Senior JH. Medical applications of multivesicular lipid-based particles: DepoFoamTM encapsulated drugs, in Medical Applications of Liposomes (Lasic DD, Papahadjopoulos D, eds). Elsevier Science B.V., New York, 1998, pp 733–750.

    Chapter  Google Scholar 

  30. Johnson EM, Ojwang JO, Szekely A, Wallace TL, Warnock DW. Comparison of in vitro antifungal activities of free and liposome-encapsulated nystatin with those of four amphotericin B formulations. Antimicrob Agents Chemother 1998; 42:1412–1416.

    PubMed  CAS  Google Scholar 

  31. Woodle MC, Matthay KK, Newman MS, et al. Versatility in lipid compositions showing prolonged circulation with sterically stabilized liposomes. Biochim Biophys Acta 1992: 1105:193–200.

    Article  PubMed  CAS  Google Scholar 

  32. Ahl PL, Bhatia SK, Meers P, et al. Enhancement of the in vivo circulation lifetime of L-alpha-distearoylphosphatidylcholine liposomes: importance of liposomal aggregation versus complement opsonization. Biochim Biophys Acta 1997; 1329:370–382.

    Article  PubMed  CAS  Google Scholar 

  33. Senior J, Crawley JCW, Gregoriadis G. Tissue distribution of liposomes exhibiting long half-lives in the circulation after intravenous injection. Biochim Biophys Acta 1985; 839:1–8.

    Article  PubMed  CAS  Google Scholar 

  34. Gabizon A, Papahadjopoulos D. Liposome formulations with prolonged circulation time in blood and enhanced uptake in tumors. Proc Natl Acad Sci USA 1988; 85:6949–6953.

    Article  PubMed  CAS  Google Scholar 

  35. Allen TM, 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; 1066:29–36.

    Article  PubMed  CAS  Google Scholar 

  36. Gabizon A, Chemla M, Tzemach D, Horowitz AT, Goren D. Liposome longevity and stability in circulation: effects on the in vivo delivery to tumors and therapeutic efficacy of encapsulated anthracyclines. J Drug Target 1996; 3:391–398.

    Article  PubMed  CAS  Google Scholar 

  37. Gregoriadis G, Senior J. The phospholipid component of small unilamellar liposomes controls the rate of clearance of entrapped solutes from the circulation. FEBS Lett 1980; 119:43–46.

    Article  PubMed  CAS  Google Scholar 

  38. Patel HM. Serum opsonins and liposomes: their interaction and opsonophagocytosis. CRC Crit Rev Therap Drug Carrier System 1992; 9:39–90.

    CAS  Google Scholar 

  39. Semple SC, Chonn A. Liposome-blood protein interactions in relation to liposome clearance. J Liposome Res 1996; 6:33–60.

    Article  CAS  Google Scholar 

  40. Moghimi SM, Patel HM. Serum opsonins and phagocytosis of saturated and unsaturated phospholipid liposomes. Biochim Biophys Acta 1989; 984:384–387.

    Article  PubMed  CAS  Google Scholar 

  41. Allen TM. A study of phospholipid interactions between lugh-density lipoproteins ana small unilamellar vesicles. Biochim Biophys Acta 1981;640:385–397.

    Article  PubMed  CAS  Google Scholar 

  42. Damen J, Regts J, Scherphof G. Transfer and exchange of pflospholipid between smaii unilamellar liposomes and rat plasma high density lipoproteins: dependence on cholesterol content and phospholipid composition. Biochim Biophys Acta 1981;665:538–545.

    Article  PubMed  CAS  Google Scholar 

  43. Allen TM. The use of glycolipids and hydrophilic polymers in avoiding rapid uptake of liposomes by the mononuclear phagocyte system. Adv Drug Del Rev 1994; 13:285–309.

    Article  CAS  Google Scholar 

  44. Klibanov AL, Maruyama K, Beckerleg AM, Torchillin VP, Huang L. Activity or amphipaihic poly(ethylene glycol) 5000 to prolong the circulation time of liposomes depends on the liposome size and is unfavorable for immunoliposomes binding to target. Biochim Biophys Acta 1991; 1062:142–148.

    Article  PubMed  CAS  Google Scholar 

  45. Lasic DD, Martin FJ, Gabizon A, Huang SK, Papahadiopoulos D. Tencally stabinzeu nposomes. hypothesis on the molecular origin of the extended circulation times. Biochim Biophys Acta 1991; 1070:187–192.

    Article  PubMed  CAS  Google Scholar 

  46. Needham DKH, McIntosh TJ, Dewhirst M, Lasic DD. Polymer-gratted liposome: pnysicai oasis forthe “stealth” property. J Liposome Res 1992; 2:411–430.

    Article  CAS  Google Scholar 

  47. Needham D, Zhelev DV, McIntosh TJ. Surface chemistry of the stencally stabilized PEu-liposome, in Liposomes: Rational Design (Janoff AS, ed). Marcel Dekker, New York, 1999, pp 13–62.

    Google Scholar 

  48. Barenholz Y, Cohen R. Rational design of amphiphile-based drug carriers and stencally stabilizea carriers. J Liposome Res 1995; 5:905–932.

    Article  CAS  Google Scholar 

  49. Lasic DD, Ceh B, Stuart MCA, Guo L, Frederik PM, Barenholz Y. Transmembrane gradient driven phase transitions within vesicles: lessons for drug delivery. Biochim Biophys Acta 1995; 1239:145–156.

    Article  PubMed  Google Scholar 

  50. Haran G, Cohen R, Bar LK, Barenholz Y. Transmembrane ammonium stlfate gradients i lipusoes produce efficient and stable entrapment of amphiphathic weak bases. Biochim Biophys Acta 1993; 1151:201–215.

    Article  PubMed  CAS  Google Scholar 

  51. Fenske DB, Wong KF, Maurer E, et al. Ionophore-mediated uptake of ciprotloxacin and vincnstine into large unilamellar vesicles exhibiting transmembrane ion gradients. Biochim Biophys Acta 1998; 1414:188–204.

    Article  PubMed  CAS  Google Scholar 

  52. Cullis PR, Hope MJ, Bally MB, Madden TD, Mayer LD, Fenske DB. Influence of pH gradients on the transbilayer transport of drugs, lipids, peptides and metal ions into large unilamellar vesicles. Biochim Biophys Acta 1997; 1331:187–211.

    Article  PubMed  CAS  Google Scholar 

  53. Madden TD, Harrigan PR, Tai LCL, et al. The accumulation of drugs within large unilamellar vesicles exhibiting a proton gradient: a survey. Chem Phys Lipids 1990; 53:37–46.

    Article  PubMed  CAS  Google Scholar 

  54. Mayer LD, Bally MB, Hope MJ, Lullí PR. Uptake or antineopiastic agen Ls int large uiaelar vesicles in response to a membrane potential. Biochim Biophys Acta 1985; 816:294–302.

    Article  PubMed  CAS  Google Scholar 

  55. Bally MB, Nayar R, Masin D, Hope MJ, Cullis PR, Mayer L. Liposomes witn entrapped doxorubicin exhibit extended blood residence times. Biochim Biophys Acta 1990; 1023:133–139.

    Article  PubMed  CAS  Google Scholar 

  56. Gabizon AA, Barenholz Y, Bialer M. Proiongation of me circulation time of dxo uii ecapulated in liposomes containing polyethylene glycol-derivatized phospholipid: pharmacokinetic studies in rodents and dogs. Pharm Res 1993; 10:703–708.

    Article  PubMed  CAS  Google Scholar 

  57. Allison BA, Pritchard PH, Richter AM, Levy JG. lhe piasma aistribution or oenzopor ucrivafive and the effects of plasma lipoproteins on its biodistribution. Photochem Photobiol 1990; 52:501–507.

    Article  PubMed  CAS  Google Scholar 

  58. Sharma A, Sharma US, Straubinger RM. H’aclitaxel-liposomes for intracavitary tnerapy of intr apciitoneal P388 leukemia. Cancer Lett 1996; 107:265–272.

    Article  PubMed  CAS  Google Scholar 

  59. Sharma A, Mayhew E, Bolcsak L, Cavanaugh C, Harmon P. Activity of paciitaxel iiposome formulations against human ovarian tumor xenografts. Int J Cancer 1997; 71:103–107.

    Article  PubMed  CAS  Google Scholar 

  60. Reddi E. Role of delivery vehicles for photosensitizers in the photodynamic therapy or tumors. .J Photochem Photobiol B: Biol 1997; 37:189–95.

    Article  CAS  Google Scholar 

  61. Ramaswamy M, Wallace TL, Cossum PA, Wasan KM. Species differences in the proportion of plasma lipoprotein lipid carried by high-density lipoproteins influence the distribution of free and liposomal nystatin in human, dog, and rat plasma. Antimicrob Agents Chemother 1999; 43:1424–1428.

    PubMed  CAS  Google Scholar 

  62. Zignani M, Drummond DC, Meyer O, Hong K, Leroux JC. In vitro characterization of a novel polymeric-based pH-sensitive liposome system. Biochim Biophvs Acta 2000: 1463:383–394.

    Article  CAS  Google Scholar 

  63. Düüzgüünes N, Straubinger RM, Baldwin PA, Papahadjopoulos D. pH-Sensitive Liposomes: Introduction of foreign substances into cells, in Membrane Fusion (Wilschut J, Hoekstra D, eds). Marcel Dekker, New York, 1991, pp 713–730.

    Google Scholar 

  64. Litzinger DC, Huang L. Phosphatidylethanolamine liposomes: drug delivery, gene transfer, and immunodiagnostic applications. Biochim Biophys Acta 1992; 1113:201–227.

    Article  PubMed  CAS  Google Scholar 

  65. Torchilin VP, Zhou F, Huang L. pH-Sensitive liposomes. J Liposome Res 1993; 3.201–255

    Article  CAS  Google Scholar 

  66. Huang SK, Stauffer PR, Hong K, et al. Liposomes and hyperthermia in mice: increased tumor uptake and therapeutic efficacy of doxorubicin in sterically stabilized liposomes. Cancer Res 1994; 54:2186–2191.

    PubMed  CAS  Google Scholar 

  67. Gaber MH, Wu NZ, Hong K, Huang SK, Dewhirst MW, Papahadjopoulos D. Thermosensitive liposomes: extravasation and release of contents in tumor microvascular networks. Int J Radiat Oncol Biol Phys 1996; 36:1177–1187.

    Article  PubMed  CAS  Google Scholar 

  68. Gaber MH, Hong K, Huang SK, Papahadjopoulos D. Thermosensitive sterically stabilized liposomes: formulation and in vitro studies on the mechanism of doxorubicin release by bovine serum and human plasma. Pharm Res 1995; 12:1407–1416.

    Article  PubMed  CAS  Google Scholar 

  69. Wiley JS, Jones SP, Sawyer WH, Paterson ARP. Cytosine arabinoside influx and nucleoside transport sites in acute leukemia. J Clin Invest 1982; 69:479–489.

    Article  PubMed  CAS  Google Scholar 

  70. Plageman PGW, Marz R, Wohlhueter RM. Transport and metabolism of deoxycytidine and 1-β-Darabinofuranosyl-cytosine into cultured Novikoff rap hepatoma cells, relationship to phosphorylation, and regulation of triphosphate synthesis. Cancer Res 1978; 38:978–989.

    Google Scholar 

  71. Westerhof GR, Rijnboutt S, Schornagel JH, Pinedo HM, Peters GJ, Jansen G. Functional activity of the reduced folate carrier in KB, MA104, and IGROV-I cells expressing folate binding protein. Cancer Res 1995; 55:3795–3802.

    PubMed  CAS  Google Scholar 

  72. Westerhof GR, Jansen G, van Emmerik N, et al. Membrane transport of natural folates and antifolate compounds in murine L1210 Leukemia cells: role of carrier- and receptor-mediated transport systems Cancer Res 1991; 51:5507–5513.

    PubMed  CAS  Google Scholar 

  73. Webb MS, Harasym TO, Masin D, Bally MB, Mayer LD. Sphingomyelin-cholesterol liposomes significantly enhance the pharmacokinetic and therapeutic properties of vincristine in murine and human tumour models. Br J Cancer 1995: 72:896–904.

    Article  PubMed  CAS  Google Scholar 

  74. Li X, Cabral-Lilly D, Janoff AS, Perkins WR. Complexation of internalized doxorubicin into fiber bundles affects its release rate from liposomes. J Liposome Res 2000: 10:15–27.

    Article  CAS  Google Scholar 

  75. Maurer-Spurej E, Wong KKF, Maurer N, Fenske DB, Cullis PR. Factors influencing uptake and retention of amino-containing drugs in large unilamellar vesicles exhibiting transmembrane pH gradients. Biochim Biophys Acta 1999; 1416:1–10.

    Article  PubMed  CAS  Google Scholar 

  76. Mui BL-S, Cullis PR, Pritchard PH, Madden TD. Influence of plasma on the osmotic sensitivity of large unilamellar vesicles prepared by extrusion. J Biol Chem 1994; 269:7364–7370.

    PubMed  CAS  Google Scholar 

  77. Adlakha-Hutcheon G, Bally MB, Shew CR, Madden TD. Controlled destabilization of a liposomal drug delivery system enhances mitoxantrone antitumor activity. Nature Biotech 1999: 17:775–779

    Article  CAS  Google Scholar 

  78. Kirpotin D, Hong K, Mullah N, Papahadjopoulos D, Zalipsky S. Liposomes with detachable polymer coating: destabilization and fusion of dioleoylphosphatidylethanolamine vesicles triggered by cleavage of surface-grafted poly(ethylene glycol). FEBS Lett 1996; 388:115–118.

    Article  PubMed  CAS  Google Scholar 

  79. Zalipsky S, Qazen M, Walker JA, 2nd, Mullah N, Quinn YP, Huang SK. New detachable poly(ethylene glycol) conjugates: cysteine-cleavable lipopolymers regenerating natural phospholipid, diacyl phosphatidylethanolamine. Bioconj Chem 1999; 10:703–707.

    Article  CAS  Google Scholar 

  80. Pak CC, Erukulla RK, Ahl PL, Janoff AS, Meers P. Elastase activated liposomal delivery to nucleated cells. Biochim Biophys Acta 1999; 1419:111–126.

    Article  PubMed  CAS  Google Scholar 

  81. Mayhew EG, Lasic D, Babbar S, Martin FJ. Pharmacokinetics and antitumor activity of epirubicin encapsulated in long-circulating liposomes incorporating a polyethlene glycol-derivatized phospholipid. Int J Cancer 1992; 51:302–309.

    Article  PubMed  CAS  Google Scholar 

  82. Working PK, Dayan AD. Pharmacological-toxicological expert report — CaelyxTM. (Stealth® liposomal doxorubicin HC1) — Foreword. Hum Exp Toxicol 1996: 15:751–785.

    PubMed  CAS  Google Scholar 

  83. Parr MJ, Masin D, Cullis PR, Bally MB. Accumulation of liposomal lipid and encapsulated doxorubicin in murine lewis lung carcinoma: the lack of beneficial effects of coating liposomes with poly(ethylene glycol). J Pharmacol Exp Therapeut 1997; 280:1319–1327.

    CAS  Google Scholar 

  84. Cowens JW, Creaven PJ, Greco WR, et al. Initial clinical (phase I) trial of TLC D-99 (doxorubicin encapsulated in liposomes). Cancer Res 1993; 53:2796–2802.

    PubMed  CAS  Google Scholar 

  85. Gill PS, Espina BM, Muggia F, Cabriales S, Tulpule A, Esplin JA, Phase I/II clinical and pharmacokinetic evaluation of liposomal daunorubicin. J Clin Oncol 1995; 13:996–1003.

    PubMed  CAS  Google Scholar 

  86. Northfelt DW, Martin FJ, Working P, et al. Doxorubicin encapsulated in liposomes containing surface-bound polyethylene glycol: pharmacokinetics, tumor localization, and safety in patients with AIDS-related Kaposi’s Sarcoma. J Clin Pharmacol 1996; 36:55–63.

    PubMed  CAS  Google Scholar 

  87. Gabizon A, Goren D, Horowitz Al Tzemach D, Lossos A, Siegai I. Long-circulating liposomes for drug delivery in cancer therapy: A review of biodistribution studies in tumor-bearing animals. Adv Drug Del Rev 1997; 24:337–344.

    Article  CAS  Google Scholar 

  88. Forssen EA, Coulter DM, Proffitt RT. Selective in vivo localization of daunorubicin small unilamellar vesicles in solid tumors. Cancer Res 1992; 52:3255–3261.

    PubMed  CAS  Google Scholar 

  89. Huang SK, Mayhew E, Gilani S, Lasic DD, Martin FJ, Papahadjopoulos D. Pharmacokinetics ana therapeutics of sterically stabilized liposomes in mice bearing C-26 colon carcinoma. Cancer Res 1992; 52:6774–6781.

    PubMed  CAS  Google Scholar 

  90. Mayer LD, Tai LCL, Ko DSC, et al. Influence ot vesicle size, lipia composition, ana arug-to-upiu ratio on the biological activity of liposomal doxorubicin in mice. Cancer Res 1989; 49:5922–5930.

    PubMed  CAS  Google Scholar 

  91. Laverman P, Boerman OC, Oyen, WJG, Dams ETM, Storm G, Corstens FHM. Liposomes tor scintigraphic detection of infection and inflammation. Adv Drug Del Rev 1999;37:225–235.

    Article  CAS  Google Scholar 

  92. Bakker-Woudenberg IAJM, Lokerse AF, Kate MTt, Storm G. Enhanced localization or liposomes with prolonged blood circulation time in infected lung tissue. Biochim Biophys Acta 1992; 1138:318–326.

    Article  PubMed  CAS  Google Scholar 

  93. Oyen WJG, Boerman OC, storm u, et al. vetecting iniection anu inflamlaLio Wit teietium99m-labeled Stealth® liposomes. J Nucl Med 1996; 37:1392–1397.

    PubMed  CAS  Google Scholar 

  94. Jain RK. Delivery of molecular medicine to solid tumors. Science 1996; 27 1:1079–1080.

    Article  Google Scholar 

  95. Huang SK, Lee K-D, Hong K, Friend DS, Papahadjopoulos D. Microscopic localization ot sterically stabilized liposomes in colon carcinoma-bearing mice. Cancer Res 1992; 52:5135–5143.

    PubMed  CAS  Google Scholar 

  96. Matsumura Y, Maeda H. A new concept for macromolecular therapeutics in r c;eothieiapy. mechanism of tumoritropic accumulation of proteins and the antitumor agent. SMANCS Cancer Res 1986; 46:6387–6392.

    PubMed  CAS  Google Scholar 

  97. Maeda H, Matsumura Y. Tumoritropic and lymphotropic principles of macromolecular drugs. CRC Crit Rev Therap Drug Carrier Syst 1989; 6:193–210.

    CAS  Google Scholar 

  98. Mayer LD, Dougherty G, Harasym TO, Bally MB. The role ot tumor-associatea macropnages in me delivery of liposomal doxorubicin to solid murine fibroscarcoma tumors. J Pharmacol Exp Therapeut 1997; 280:1406–1414.

    CAS  Google Scholar 

  99. Mayer LD, Cullis PR, Bally MB. Designing therapeutically optimized liposomal anticancer delivery systems: lessons from conventional liposomes, in Medical Applications of Liposomes (Papahadjopoulos LA, ed). Elsevier Science B.V., New York, 1998.

    Google Scholar 

  100. Harasym TO Lullis PK, Bally NIB. intratumor aistrioution of foxorubici fwin . v. aumuiisu ation of drug encapsulated in egg phophatidylcholine/cholesterol liposomes. Cancer Chemother Pharmacol 1997; 40:309–317.

    Article  Google Scholar 

  101. Siegal T, Horowitz A, Gabizon A. Doxorubicin encapsulated in sterically stabilized liposomes for the treatment of a brain tumor model: biodistribution and therapeutic efficacy. J Neurosurg 1995; 83:1029–1037.

    Article  PubMed  CAS  Google Scholar 

  102. Goren D, Horowitz AT, Zalipsky S, Woodle MC, Yarden Y, Gabizon A. largeting of stealth uposomes to erbB-2 (Her/2) receptor: In vitro and in vivo studies. Br J Cancer 1996;74:1749–1756.

    Article  PubMed  CAS  Google Scholar 

  103. Krishna R, St-Louis M, Mayer LD. increased intracellular drug accumulatio ad chemosensitization achieved in multidrug-resistant solid tumors by co-administering valspodar (PSC 833) with sterically stabilized liposomal doxorubicin. Int J Cancer 2000; 85:131–141.

    Article  PubMed  CAS  Google Scholar 

  104. Allen TM, Mehra T, Hansen C, Chin Y C. Stealth liposomes: an improved sustained release syste for 1-β-D-arabinofuranosy1cytosine. Cancer Res 1992; 52:2431–2439.

    PubMed  CAS  Google Scholar 

  105. Colbern GT, Dykes DJ, Engbers C, et al. Encapsulation of the topoisomerase I inhibitor UL14 / L1 IL in pegylated (STEALTH) liposomes: pharmacokinetics and antitumor activity in HT29 colon tumor xenografts. Clin Cancer Res 1998; 4:3077–3082.

    PubMed  CAS  Google Scholar 

  106. Cabanes A, Even-Chen S, Zimberoff J, Barenholz Y, Kedar E, Gabizon A. Enhancement of antitumor activity of polyethylene glycol-coated liposomal doxorubicin with soluble and liposomal interleukin 2. Clin Cancer Res 1999; 5:687–693.

    PubMed  CAS  Google Scholar 

  107. Newman MS, Colbern GT, Working PK, Engbers C, Amantea M. Comparative pharmacokinetics, tissue distribution, and therapeutic effectiveness of cisplatin encapsulated in long-circulating, pegylated liposomes (SPI-077) in tumor-bearing mice. Cancer Chemother Pharmacol 1999; 43:1–7.

    Article  PubMed  CAS  Google Scholar 

  108. Colbern G, Vaage J, Donovan D, Uster P, Working P, Tumor uptake and therapeutic effects of drugs encapsulated in long-circulating pegylated STEALTH® liposomes. J Liposome Res 2000; 10:81–92.

    Article  CAS  Google Scholar 

  109. Unezaki S, Mauryama K, Ishida O, Suginaka A, Junichi H, Iwatsuru M. Enhanced tumor targeting and improved antitumor activity of doxorubicin by long-circulating liposomes containing amphipathic poly(ethylene glycol). Int J Pharmaceut 1995; 126:41–48.

    Article  CAS  Google Scholar 

  110. Chang CW, Barber L, Ouyang C, Masin D, Bally MB, Madden TD. Plasma clearance, biodistribution and therapeutic properties of mitoxantrone encapsulated in conventional and sterically stabilized liposomes after intraveneous administration in BDF1 mice. Br J Cancer 1997; 75:169–177.

    Article  PubMed  CAS  Google Scholar 

  111. Doroshaw JH, Anthracyclines and antracenediones, in Cancer chemotherapy and biotherapy: principles and practice (Chabner BA, Longo DL, eds). Lippincott-Raven, Philadelphia 1996 pp 409–433.

    Google Scholar 

  112. Young RC, Ozols RF, Myers CE. The anthracycline antineoplastic drugs. N Engl J Med 1981; 305:139–153.

    Article  PubMed  CAS  Google Scholar 

  113. Sarris AH, Hagemeister F, Romaguera J, et al. Liposomal vincristine in relapsed non-Hodgkin’s lymphomas: early results of an ongoing phase II trial. Ann Oncol 2000; 11:69–72.

    Article  PubMed  CAS  Google Scholar 

  114. Kruszewski S, Chavan AS, Grycynski I, Lakowicz JR, Burke TG. Comparison of the human blood chemistry of free versus liposomal forms of the clinically-relevant topoisomerase I inhibitor lurtotecan (GI147221). Am Assoc Cancer Res 2000; 41:A2056.

    Google Scholar 

  115. Gelmon KA, Eisenhauer E, Renyo L, et al. Phase I study of NX211 (liposomal lurtotecan) given as an intravenous infusion on days 1 2 &3 every 3 weeks in patients with solid tumors- and NCIC Clinical Trials Group study. Am Assoc Cancer Res 2000; 41:A3879.

    Google Scholar 

  116. Amantea MA, Forrest A, Northfelt DW, Mamelok R. Population pharmacokinetics and pharmacodynamics of pegylated-liposomal doxorubicin in patients with AIDS-related Kaposi’s sarcoma. Clin Pharmacol Therap 1997; 61:301–311.

    Article  CAS  Google Scholar 

  117. Gill PS, Wernz J, Scadden DT, et al. Randomized phase III trial of liposomal daunorubicin versus doxorubicin, bleomycin, and vincristine in AIDS-related Kaposi’s sarcoma. J Clin Oncol 1996; 14:2353–2364.

    PubMed  CAS  Google Scholar 

  118. Girard PM, Bouchaud O, Goetschel A, Mukwaya G, Eestermans G, Ross M. Phase II study of liposomal encapsulated daunorubicin in the treatment of AIDS-associated mucocutaneous Kaposi’s sarcoma. Aids 1996; 10:753–757.

    Article  PubMed  CAS  Google Scholar 

  119. Presant CA, Scolaro M, Kennedy P, et al. Liposomal daunorubicin treatment of HIV-associated Kaposi’s sarcoma. Lancet 1993; 341:1242–1243.

    Article  PubMed  CAS  Google Scholar 

  120. Tulpule A, Yung RC, Wernz J, et al. Phase II trial of liposomal daunorubicin in the treatment of AID Srelated pulmonary Kaposi’s sarcoma. J Clin Oncol 1998; 16:3369–3374.

    PubMed  CAS  Google Scholar 

  121. Harrison M, Tomlinson D, Stewart S. Liposomal-entrapped doxorubicin: an active agent in AIDSrelated Kaposi’s sarcoma. J Clin Oncol 1995; 13:914–920.

    PubMed  CAS  Google Scholar 

  122. Ranson MR, Carmichael J, O’Byrne K, Stewart S, Smith D, Howell A. Treatment of advanced breast cancer with sterically stabilized liposomal doxorubicin: results of a multicenter phase II trial. J Clin Oncol 1997; 15:3185–3191.

    PubMed  CAS  Google Scholar 

  123. Muggia FM. Clinical efficacy and prospects for use of pegylated liposomal doxorubicin in the treatment of ovarian and breast cancers. Drugs 1997; 54:22–29.

    Article  PubMed  CAS  Google Scholar 

  124. Muggia FM, Hainsworth JD, Jeffers S, et al. Phase II study of liposomal doxorubicin in refactory ovarian cancer: antitumor activity and toxicity modification by liposomal encapsulation. J Clin Oncol 1997; 15:987–993.

    PubMed  CAS  Google Scholar 

  125. Alberts DS, Garcia DJ. Safety aspects of pegylated liposomal doxorubicin in patients with cancer. Drugs 1997; 54 Suppl. 4:30–35.

    Article  PubMed  CAS  Google Scholar 

  126. Symon Z, Peyser A, Tzemach D, et al. Selective delivery of doxorubicin to patients with breast carcinoma metastases by stealth liposomes. Cancer 1999: 86:72–78.

    Article  PubMed  CAS  Google Scholar 

  127. Harris L, Winer E, Batist G, Rovira D, Navarja R, Lee L. Phase III study of TLC D-99 (liposome encapsulated doxorubicin) vs. free doxorubicin (DOX) in patients with metastatic breast carcinoma (MBC). Proc Am Soc Clin Oncol 1998; 17:124a.

    Google Scholar 

  128. Shapiro CL, Ervin T, Welles L, Azarnia N, Keating J, Hayes DF. Phase II trial of high-dose liposomeencapsulated doxorubicin with granulocyte colony-stimulating factor in metastic breast cancer. J Clin Oncol 1999; 17:1435–1441.

    PubMed  CAS  Google Scholar 

  129. Valero V, Buzdar AU, Theriault RL, et al. Phase II trial of liposome-encapsulated doxorubicin cyclophosphamide, and fluorouracil as first-line therapy in patients with metastatic breast cancer. J Clin Oncol 1999; 17:1425–1434.

    PubMed  CAS  Google Scholar 

  130. Burstein HJ, Ramirez MJ, Petros WP, et al. Phase I study of Doxil and vinorelbine in metastatic breast cancer. Ann Oncol 1999; 10:1113–1116.

    Article  PubMed  CAS  Google Scholar 

  131. Woll PJ, Carmichael J, Chan S, Howell A, Ranson M, Miles D, Welbank H. Phase II study results on safety and tolerability of caelyx® (Doxil®) in combination with paclitaxel in the treatment of metastatic breast cancer. Proc Am Soc Clin Oncol 1999; 18:A442.

    Google Scholar 

  132. Modiano M, Taylor C, Sharpington R, Ng M, Mảtinez A. Phase I study of Doxil® (pegylated liposomal doxorubicin) plus escalating doses of taxol® in the treatment of patients with advanced breast or gynecologic malignancies. Proc Am Soc Clin Oncol 1999; 18:A848.

    Google Scholar 

  133. Silverman P, Overmoyer B, Holder L, Tripathy D, Marrs N, Sharpington Doxir ana intravenous cyclophosphamide as first-line therapy for patients with metastatic breast cancer (MBC): interim results of an ongoing pilot trial. Proc Am Soc Clin Oncol 1999; 18:A435.

    Google Scholar 

  134. Garcia AA, Kempf RA, Rogers M, Muggia FM. A phase 11 study or voxii (iiposomai doxortibiein): lack of activity in poor prognosis soft tissue sarcomas. Ann Oncol 1998; 9:1131–1133.

    Article  PubMed  CAS  Google Scholar 

  135. Halm U, Etzrodt G, Schiefke I, et al. A phase II study of pegylated liposomal doxorubicin for treatment of advanced hepatocellular carcinoma. Ann Oncol 2000; 11:113–114.

    Article  PubMed  CAS  Google Scholar 

  136. Yeo W, Chan KK, Mukwaya G, et al. Phase 11 studies witn vaunoXome in patients ith nonresectable hepatocellular carcinoma: clinical and pharmacokinetic outcomes. Cancer Chemother Pharmacol 1999; 44:124–130.

    Article  PubMed  CAS  Google Scholar 

  137. Boiardi A, Pozzi A, Salmaggi A, Eoli M, Zucchetti M, Silvani A. Safety and potential effectiveness or daunorubicin-containing liposomes in patients with advanced recurrent malignant CNS tumors. Cancer Chemother Pharmacol 1999; 43:178–179.

    Article  PubMed  CAS  Google Scholar 

  138. Zucchetti M, Boiardi A, Silvani A, Parisi I, Piccolrovazzi S, Dincalci M. Distribution of daunorubicin and daunorubicinol in human glioma tumors after administration of liposomal daunorubicin. Cancer Chemother Pharmacol 1999; 44:173–176.

    Article  PubMed  CAS  Google Scholar 

  139. Koukourakis MI, Koukouraki S, Giatromanolaki A, et al. Liposomal doxorubicin ana conventionally fractionated radiotherapy in the treatment of locally advanced non-small-cell lung cancer and head and neck cancer. J Clin Oncol 1999; 17:3512–3521.

    PubMed  CAS  Google Scholar 

  140. Kirpotin DB, Park JW, Demetzos K, et al. Stealtt® liposomal vinorelbine: synthesis stabinty mor activity against human breast and lung cancer xenografts. Proc Am Assoc Cancer Res 1999a; 40:417.

    Google Scholar 

  141. Working PK, Newman MS, Sullivan T, Yarrington J. Reduction of the cardiotoxicity of doxorubicin in rabbits and dogs by encapsulation in long-circulating, pegylated liposomes. J Pharmacol Exp Therap 1999; 289:1128–1133.

    CAS  Google Scholar 

  142. Von Hoff DD, Layard MW, Basa P, et al. Risk factors for doxorubicin-induced congestive neart failure. Ann Intern Medicine 1979; 91:710–717.

    Google Scholar 

  143. Legha SS, Hortobagyi GN, Benjamin KS. Anthracyclines, in cancer Cnemotherapy by irf us iun (Lokich JJ, ed). 1 Ed. Precept Press, Inc. Chicago, 1987, pp 130–144.

    Google Scholar 

  144. Speth PAJ, van Hoesel QGCM, Haanen C. Clinical pharmacokinetics or doxorunicin. lin rnarmacokin 1988; 15:15–31.

    CAS  Google Scholar 

  145. Working PK, Newman MS, Huang SK, Mayhew E, Vaage J, Lasic DD. Pharmacokinetics, biodistribution, and therapeutic efficacy of doxorubicin encapsulated in Stealth® liposomes (Doxi1®). J Liposome Res 1994; 4:667–687.

    Article  Google Scholar 

  146. Casper ES, Schwartz GK, Sugarman A, Leung D, Brennan ME Phase I trial of dose-intense liposomeencapsulated doxorubicin in patients with advanced sarcoma. J Clin Oncol 1997; 15:2111–2117.

    PubMed  CAS  Google Scholar 

  147. Kanter PM, Bullard GA, Ginsberg RA, et al. Comparison of the cardiotoxic effects or liposomai doxorubicin (TLC D-99) versus free doxorubicin in beagle dogs In vivo. 1993; 7:17–26.

    PubMed  CAS  Google Scholar 

  148. Conley BA, Egorin MJ, Whitacre MY, Carter VU, Lunowski EG. rnase I anu pnarimaeukinctictial o liposome-encapsulated doxorubicin. Cancer Chemother Pharmacol 1993; 33:107–112.

    Article  PubMed  CAS  Google Scholar 

  149. Bally MB, Nayar R, Masin D, Cullis PR, Mayer LD. Studies on tne myeiosuppresive activity or doxorubicin entrapped in liposomes. Cancer Chemother Pharmacol 1990; 27:13–19.

    Article  PubMed  CAS  Google Scholar 

  150. Oussoren C, Eling WMC, Crommelin DJA, Storm G, Zuidema J. The influence of the route of aaministration and liposome composition on the potential of liposomes to protect tissue against local toxicity of two antitumor drugs. Biochim Biophys Acta 1998;1369:l59-l72.

    Google Scholar 

  151. Perkins WR, Dause RB, Li X, et al. Combination or antitumor etner lipid wan ipius of compementary molecular shapes reduces its hemolytic activity. Biochim Biophys Acta 1997; 1327:61–68.

    Article  PubMed  CAS  Google Scholar 

  152. Ahmad I, Filep JJ, Franklin JC, et al. Enhanced therapeutic effects of liposome-associated Octadecy1–2-O-methyl-sn-glycero-3-phosphocholine. Cancer Res 1997; 57:1915–1921.

    PubMed  CAS  Google Scholar 

  153. White RM. Liposomal daunorubicin is not recommended in patients with less than advanced HIVrelated Kaposi’s sarcoma. Aids 1997; 11:1412–1413.

    Article  PubMed  CAS  Google Scholar 

  154. Allen TM, Murray L, MacKeigan S, Shah M. unronic iiposome aarrinistrauon i iee. CfIeLs reticuloendothelial function and tissue distribution. J Pharmacol Exp Therap 1984; 229:267–275.

    CAS  Google Scholar 

  155. Daemen T, Hofstede G, Kate MTT, Bakker-Woudenberg IAJM, Scherphof G. Liposomal doxorubicin-induced toxicity: depletion and impairment of phagocytic activity of liver macrophages. Int J Cancer 1995; 61:716–721.

    Article  PubMed  CAS  Google Scholar 

  156. Daemen T, Regts J, Meesters M, Ten Kate MT, Bakker-Woudenberg IAJM, Scherphof GL. Toxicity of doxorubicin entrapped within long-circulating liposomes. J Controlled Release 1997; 44:1–9.

    Article  CAS  Google Scholar 

  157. Gabizon A, Isacson R, Libson E, et al. Clinical studies of liposome-encapsulated doxorubicin. Acta Oncol 1994; 33:779–786.

    Article  PubMed  CAS  Google Scholar 

  158. Uziely B, Jeffers S, Isacson R, et al. Liposomal doxorubicin: antitumor activity and unique toxicities during two complementary phase I studies. J Clin Oncol 1995; 13:1777–1785.

    PubMed  CAS  Google Scholar 

  159. Amantea M, Newman MS, Sullivan TM, Forrest A, Working PK. Relationship of dose intensity to the induction of palmar-plantar erythrodysesthia by pegylated doxorubicin in dogs. Hum Exp Toxicol 1999: 18:17–26

    Article  PubMed  CAS  Google Scholar 

  160. Lokich JJ, Moore C. Chemotherapy-associated palmar-plantar erythrodysesthesia syndrome. Ann Intern Med 1984; 101:798–800.

    PubMed  CAS  Google Scholar 

  161. Vogelzang NJ, Ratain MJ. Cancer chemotherapy and skin changes. Ann Intern Med 1985; 103:303–304.

    PubMed  CAS  Google Scholar 

  162. Allen TM, Hansen CB, Stuart DD. Targeted sterically stabilized liposomal drug delivery, in Medical Applications of Liposomes (Lasic DD, Papahadjopoulos D, eds). Elsevier Science B.V., New York, 1998, pp 545–565.

    Google Scholar 

  163. Ahmad I, Longenecker M, Samuel J, Allen TM. Antibody-targeted delivery of doxorubicin entrapped in sterically stabilized liposomes can eradicate lung cancer in mice. Cancer Res 1993; 53:1484–1488.

    PubMed  CAS  Google Scholar 

  164. Lopes de Menezes DE, Pilarski LM, Allen TM. In vitro and in vivo targeting of immunoliposomal doxorubicin to human B-cell lymphoma. Cancer Res 1998; 58:3320–3330.

    Google Scholar 

  165. Park JW, Hong K, Carter P, et al. Development of anti-p185HER2 immunoliposomes for cancer therapy. Proc Natl Acad Sci USA 1995; 92:1327–1331.

    Article  PubMed  CAS  Google Scholar 

  166. Tseng Y-L, Hong R-L, Tao M-H, Chang F-H. Sterically stabilized anti-idiotype immunoliposomes improve the therapeutic efficacy of doxorubicin in a murine B-cell lymphoma model. Int J Cancer 1999: 80:723–730.

    Article  PubMed  CAS  Google Scholar 

  167. Lee RJ Low PS. Folate-mediated tumor cell targeting of liposome-entrapped doxorubicin in vitro. Biochim Biophys Acta 1995; 1233:134–144.

    Article  PubMed  Google Scholar 

  168. Wang S, Low PS. Folate-mediated targeting of antineoplastic drugs, imaging agents, and nucleic acids to cancer cells. J Control Rel 1998; 53:39–48.

    Article  CAS  Google Scholar 

  169. Lee RI, Low PS. Folate-targeted liposome for drug delivery. J Linosome Res 1997. 7.455–4M

    Article  CAS  Google Scholar 

  170. Drummond DC, Hong K, Park JW, Benz CC, Kirpotin DB. (2000) Liposome Targeting to Tumors Using Vitamin and Growth Factor Receptors. Vitamins and Hormones. Edited by Litwack G in press

    Google Scholar 

  171. Hansen CB, Kao GY, Moase EH, Zalipsky S, Allen TM. Attachment of antibodies to sterically stabilized liposomes: evaluation comparison and optimization of coupling procedures. Biochimica et Biophysica Acta 1995; 1239:133–144.

    Article  PubMed  Google Scholar 

  172. Zalipsky S, Gittelman J, Mullah N, Qazen MM, Harding JA. Biologically active ligand-bearing polymer-grafted liposomes, in Targeting of drugs 6: strategies for stealth therapeutic systems (Gregoriadis, G., McCormack B. eds). Plenum, New York, 1998, pp 131–138.

    Google Scholar 

  173. Zalipsky S, Mullah N, Harding JA, Gittelman J, Guo L, DeFrees SA. Poly(ethylene glycol)-grafted liposomes with oligopeptide or oligosaccharide ligands appended to the termini of the polymer chains. Bioconj Chem 1997; 8:111–118.

    Article  CAS  Google Scholar 

  174. Zalipsky S, Puntambekar B, Boulikas P, Engbers CM, Woodle MC. Peptide attachment to extremities of liposomal surface grafted PEG chains: preparation of the long-circulating form of laminin pentapeptide, YIGSR. Bioconj Chem 1995; 6:705–708.

    Article  CAS  Google Scholar 

  175. Zalipsky S, Functionalized poly(ethlene glycol) for preparation of biologically relevant conjugates. Bioconj Chem 1995; 6:150–165.

    Article  CAS  Google Scholar 

  176. Zalipsky S. Synthesis of an end-group functionalized polyethylene glycol-lipid conjugate for preparation of polymer-grafted liposomes. Bioconi Chem 1993; 4:296–299.

    Article  CAS  Google Scholar 

  177. Kirpotin D, Park JW, Hong K, et al. Sterically stabilized anti-HER2 immunoliposomes: design and targeting to human breast cancer cells in vitro. Biochemistry 1997; 36:66–75.

    Article  PubMed  CAS  Google Scholar 

  178. Lee RJ, Low PS. Delivery of liposomes into cultured KB cells via folate receptor-mediated endocytosis. J Biol Chem 1994; 269:3198–3204.

    PubMed  CAS  Google Scholar 

  179. Debs RJ, Heath TD, Papahadjopoulos D. Targeting of anti-Thy 1.1 monoclonal antibody conjugated liposomes in Thy 1.1 mice after intravenous administration. Biochim Biophys Acta 1987; 901:183–190.

    Article  PubMed  CAS  Google Scholar 

  180. Harding JA, Engbers CM, Newman MS, Goldstein NI, Zalipsky S. Immunogenicity and pharmacokinetic attributes of poly(ethyleneglycol)-grafted immunoliposomes. Biochim Biophys Acta 1997; 1327:181–192.

    Article  PubMed  CAS  Google Scholar 

  181. Allen TM, Agrawal AK, Ahmad I, Hansen CB, Zalipsky S. Antibody-mediatea targeting or long-circulating (Stealth®) liposomes. J Liposome Res 1994; 4:1–25.

    Article  CAS  Google Scholar 

  182. Allen TM, Ahmad I, Lopes de Menezes DE, Moase EH. Immunoliposome-meciated targeting or anticancer drugs in vivo. Biochem Soc Trans 1995; 23:1073–1079. .

    PubMed  CAS  Google Scholar 

  183. Mori A, Klibanov AL, Torchilin VP, Huang L. Influence of the steric barrier activity ot amphipathic poly(ethyleneglycol) and ganglioside GM1 on the circulation time of liposomes and on the target binding of immunoliposomes in vivo. FEBS Lett 1991; 284:263–266.

    Article  PubMed  CAS  Google Scholar 

  184. Zalipsky S, Hansen CB, de Menezes DEL, Allen TM. Long-circulating, polyethylene glycol-grarted immunoliposomes. J Controlled Release 1996; 39:153–161.

    Article  CAS  Google Scholar 

  185. Martin FJ, Hubbell WL, Papahadjopoulos D. Immunospecific targeting of liposomes to cells: a novel and efficient method for covalent attachment of Fab’ fragments via disulfide bonds. Biochemistry 1981; 20:4229–4238.

    Article  PubMed  CAS  Google Scholar 

  186. Martin FJ, Papahadjopoulos D. Irreversible coupling of immunoglobulin fragments to prerormea vesicles. An improved method for liposome targeting. J Biol Chem 1982; 257:286–288.

    PubMed  CAS  Google Scholar 

  187. Derksen JTP, Morselt HWM, Scherphof GL. Uptake and processing of immunoglobulin-coated liposomes by subpopulations of rat liver macrophages. Biochim Biophys Acta 1988; 971:127–136.

    Article  PubMed  CAS  Google Scholar 

  188. Aragnol D, Leserman LD. Immune clearance of liposomes inmbited by an anti-rc icccptr antiuouy in vivo. Proc Natl Acad Sci USA 1986; 83:2699–2703.

    Article  PubMed  CAS  Google Scholar 

  189. Kirpotin DB, Park JW, Hong K, et al. Targeting of sterically stabilized liposomes to cancers overex pressing HER2/neu proto-oncogene, in Medical Applications of Liposomes (Lasic DD, Papahadjopoulos D, eds). Elsevier Science B.V., New York, 1998, pp 325–345.

    Chapter  Google Scholar 

  190. Park JW, Hong K, Kirpotin DB, et al. Anti-HER2 immunoliposomes: enhanced efficacy attributable to targeted delivery. Clin Cancer Res 2002; 8:1172–1181.

    PubMed  CAS  Google Scholar 

  191. Parr MJ, Ansell SM, Choi LS, Cullis PR. Factors influencing the retention and chemical stability of poly(ethylene glycol)-lipid conjugates incorporated into large unilamellar vesicles. Biochim Biophys Acta 1994; 1195:21–30.

    Article  PubMed  CAS  Google Scholar 

  192. Scherphof GL, Kamps JAAM, Koning GA. In vivo targeting of surtace-mocified liposomes to metastatically growing carcinoma cells and sinusoidal endothelial cells in the rat liver. J Liposome Res 1997; 7:419–432.

    Article  CAS  Google Scholar 

  193. Mori A, Kennel SJ, Waalkes MvB, Scherphof GL, Huang L. Charactenzation or organ-specinc immunoliposomes for delivery of 3′,5′-O-dipalmitoy1–5-fluoro-2′-deoxyuridine in a mouse lungmetastasis model. Cancer Chemother Pharmacol 1995; 35:447–456.

    Article  PubMed  CAS  Google Scholar 

  194. Oku N, Tokudome Y, Koike C, et al. Liposomal Arg-Gly-Asp analogs effectively inhibit metastatic B16 melanoma colonization in murine lungs. Life Sci 1996; 58:2263–2270.

    Article  PubMed  CAS  Google Scholar 

  195. Fujimori K, Covell DG, Fletcher JE, Weinstein JN. A modeling analysis of monoclonal antibody percolation through tumors: a binding site barrier. J Nucl Med 1990; 31:1191–1198.

    PubMed  CAS  Google Scholar 

  196. Weinstein JN, Eger RR, Covell DU, et al. The pharmacology or monoclonal antibodies. Ann v cd Sci 1987; 507:199–210.

    CAS  Google Scholar 

  197. Jain RK. Delivery of novel therapeutic agents in tumors: physiological barriers and strategies. J Natl Cancer Inst 1989; 81:570–576.

    Article  PubMed  CAS  Google Scholar 

  198. Huang A, Kennel SJ, Huang L. Interactions of immunoliposomes with target cells. J Biol Chem 1983; 258:14,034–14,040.

    PubMed  CAS  Google Scholar 

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  1. Daryl C. Drummond PhD
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  2. Dmitri Kirpotin PhD
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  3. Christopher C. Benz MD
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    Dennis M. Brown

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Drummond, D.C., Kirpotin, D., Benz, C.C., Park, J.W., Hong, K. (2004). Liposomal Drug Delivery Systems for Cancer Therapy. In: Brown, D.M. (eds) Drug Delivery Systems in Cancer Therapy. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-427-6_9

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