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
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.
Available from: Saeed Ghanbarzadeh
- "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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ABSTRACT: The aim of this study was the design and evaluation of a novel plasma stable, pH-sensitive niosomal formulation of Mitoxantrone by a modified ethanol injection method. Cholesterol hemisuccinate was added instead of cholesterol in order to produce pH-sensitivity property and using PEG-Poly (monomethyl itaconate)-CholC6 (PEG-PMMI-CholC6) copolymer introduced simultaneously pH-sensitivity and plasma stability properties in prepared niosomes. The pH-sensitivity and cytotoxicity of Mitoxantrone niosomes were evaluated in vitro in phosphate buffer with different pHs as well as using human ovarian cancer cell line (OVCAR-3), human breast cancer cell line (MCF-7) and human umbilical vein endothelial cells (HUVEC). Results showed that both cholesterol derivatives bearing formulations had pH-sensitive property and were found to release their contents under mild acidic conditions rapidly. In addition, the PEG-PMMI-CholC6-based niosomes could reserve the pH-sensitivity after incubation in plasma. Both Mitoxantrone-loaded pH-sensitive niosomes showed higher cytotoxicity than the conventional niosomes on OVCAR-3 and MCF-7 cell lines. However, both pH-sensitive niosomes exhibited lower cytotoxic effect on HUVEC cell line. Plasma stable, pH-sensitive niosomes could improve the cytotoxic effect and reduce the side effects of anti-tumor drugs.
EXCLI Journal 01/2015; 14:21-32. DOI:10.17179/excli2013-609 · 0.86 Impact Factor
Available from: Luiz Claudio Miletti
- "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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ABSTRACT: SUMMARY This study aimed to develop and test the in vitro and in vivo effectiveness of diminazene aceturate encapsulated into liposomes (L-DMZ) on Trypanosoma evansi. To validate the in vitro tests with L-DMZ, the efficacy of a commercial formulation of diminazene aceturate (C-DMZ) was also assessed. The tests were carried out in culture medium for T. evansi, at concentrations of 0·25, 0·5, 1, 2 and 3 μg mL-1 of L-DMZ and C-DMZ. A dose-dependent effect was observed for both formulations (L-DMZ and C-DMZ), with the highest dose-dependent mortality of trypomastigotes being observed at 1 and 3 h after the onset of tests with L-DMZ. The results of in vivo tests showed the same effects in the animals treated with L-DMZ and C-DMZ in single doses of 3·5 mg kg-1 and for 5 consecutive days (3·5 mg kg-1 day-1). It was possible to conclude that T. evansi showed greater in vitro susceptibility to L-DMZ when compared with C-DMZ. In vivo tests suggest that treatment with the L-DMZ and C-DMZ showed similar efficacy in vivo. The potential of the formulation developed in this study was clearly demonstrated, as it increased the efficacy of the treatment against trypanosomosis, but more studies are needed to increase the effectiveness in vivo.
Parasitology 01/2014; 141(6):1-9. DOI:10.1017/S0031182013002114 · 2.56 Impact Factor
Available from: utoronto.ca
- "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 , dendrimers , and polymeric nanoparticles . 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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ABSTRACT: Drug delivery to solid tumours remains a challenge because both tumour physiology and drug solubility are unfavourable. Engineered materials can provide the basis for drug reformulation, incorporating active compounds and modulating their pharmacokinetic and biodistribution behaviour. To this end, we encapsulated docetaxel, a poorly soluble taxane drug, in a self-assembled polymeric nanoparticle micelle of poly(2-methyl-2-carboxytrimethylene carbonate-co-D,L-lactide)-graft-poly(ethylene glycol) (poly(TMCC-co-LA)-g-PEG). This formulation was compared with its conventional ethanolic polysorbate 80 formulation in terms of plasma circulation and biodistribution in an orthotopic mouse model of breast cancer. Notably, the polymeric nanoparticle formulation achieved greater tumour retention, resulting in prolonged exposure of cancer cells to the active drug. This behaviour was unique to the tumour tissue. The active drug was eliminated at equal or greater rates in all other tissues assayed when delivered in the polymeric nanoparticles vs. the free drug formulation. Thus, these polymeric nanoparticles are promising vehicles for solid tumour drug delivery applications, offering greater tumour exposure while eliminating the need for toxic solvents and surfactants in the dosing formulation.
Biomaterials 12/2011; 33(7):2223-9. DOI:10.1016/j.biomaterials.2011.11.072 · 8.56 Impact Factor
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