Liposome-based approaches to overcome anticancer drug resistance

Division of Hematology/Oncology, University of California, San Francisco (UCSF), 2340 Sutter Street, San Francisco, CA 94115, USA.
Drug Resistance Updates (Impact Factor: 9.12). 11/2003; 6(5):271-9. DOI: 10.1016/S1368-7646(03)00082-7
Source: PubMed


Drug resistance remains an important obstacle towards better outcomes in the treatment of cancer. One general approach to overcome this problem has been to inhibit specific resistance mechanisms, such as P-glycoprotein (PGP)-mediated drug efflux, using small molecule agents or other therapeutic strategies. Alternatively, drug delivery approaches using liposomes or other carriers can in principle target drugs to tumor tissue, tumor cells, or even compartments within tumor cells. By increasing bioavailability of drugs at sites of action, these approaches may provide therapeutic advantages, including enhanced efficacy against resistant tumors. Current liposomal anthracyclines have achieved clinical use in cancer treatment by providing efficient encapsulation of drug in stable and non-reactive carriers, and there is evidence indicating potential benefit in some clinical settings involving resistant tumors. Other liposome-based strategies include constructs designed to be taken up by tumor cells, as well as further modifications to allow triggered drug release. These approaches seek to overcome drug resistance by more efficient delivery to tumor cells, and in some cases by concomitant avoidance or inhibition of drug efflux mechanisms. Newer agents employ molecular targeting, such as immunoliposomes using antibody-directed binding and internalization. These agents selectively deliver drug to tumor cells, can efficiently internalize for intracellular drug release, and can potentially enhance both efficacy and safety.

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    • "High drug toxicity is a drawback for dose of chemotherapeutics, because side effects limit the drug dosage that can be administered (Hrushesky et al., 1992; Wong et al., 2007). Vesicles are promising carriers employed to deliver chemotherapeutic agents, antisense oligonucleotides and genes to various therapeutic targets , specifically (Chen et al., 2010; Gabizon et al., 2004; Mamot et al., 2003; Petersen et al., 2012). However, significant progress in overcoming many of the original obstacles for effective delivery of these agents has been limited. "
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    EXCLI Journal 01/2015; 14:21-32. DOI:10.17179/excli2013-609 · 0.86 Impact Factor
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    • "Among the nanostructure systems are the liposomes, which are vesicles that consist of one or more phospholipid bilayers that surround an aqueous compartment, serving as drug carriers, biomolecules or diagnostic agents (Batista, 2007). They are used as an alternative in reducing systemic toxicity and cytotoxicity to normal cells, side effects associated with chemotherapy, since they are able to change the pharmacokinetics and biodistribution of antineoplastic drugs (Immordino et al. 2003; Mamot et al. 2003). The treatment of trypanosomosis is based on specific drugs such as suramin, diminazene, quinapyramine, melarsoprol, homidium and isometamidium. "
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    Parasitology 01/2014; 141(6):1-9. DOI:10.1017/S0031182013002114 · 2.56 Impact Factor
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    • "Well-designed nanoscale drug delivery systems have the potential to increase the therapeutic index of small molecule drugs by extending drug circulation while boosting solid tumour specificity and accumulation through the EPR effect. To take advantage of EPR, several technologies have been developed, including liposomes [7], dendrimers [8], and polymeric nanoparticles [9]. Polymeric nanoparticles, comprised of a hydrophobic core and hydrophilic corona, are particularly compelling for the encapsulation and delivery of hydrophobic and poorly water soluble chemotherapeutic drugs. "
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