Applications of Liposome Technology to Overcome Multidrug Resistance in Solid Tumors

  • Rajesh Krishna
  • Lawrence D. Mayer
Part of the NATO ASI Series book series (NSSA, volume 300)


A significant obstacle to chemotherapy of many human malignancies is the development of drug resistance. Multidrug resistance (MDR) is defined as the ability of tumor cells to develop resistance to the cytotoxic effects of a variety of chemically unrelated chemotherapeutic agents. Several mechanisms have been proposed to explain this phenomenon; however, the P-glycoprotein (PGP) based MDR phenotype has received the most attention and has been correlated with poor patient outcome for a number of tumor types. Conventional strategies employed for overcoming MDR involve the use of a PGP inhibitor coadministered with the anticancer agent. However, progress in this area has been hindered by the relatively low specificity of PGP modulators for tumor tissue. This has resulted in problems associated with inherent modulator toxicity as well as modulator induced changes in anticancer drug pharmacokinetics. Several avenues have been pursued using liposome technology to overcome these difficulties. This review summarizes some of the work done in this area and how long circulating non-leaky liposomes may be applied to circumvent adverse drug-drug interactions between MDR modulators and anticancer drugs, resulting in effective therapy of MDR in solid tumors.


Anticancer Drug Multidrug Resistance Maximum Tolerate Dose Liposomal Doxorubicin Residual Resistance Factor 
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Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Rajesh Krishna
    • 1
    • 2
  • Lawrence D. Mayer
    • 1
    • 2
  1. 1.Department of Advanced TherapeuticsBC Cancer AgencyVancouverCanada
  2. 2.Faculty of Pharmaceutical SciencesUniversity of British ColumbiaVancouverCanada

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