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Review
. 2013 Nov;65(13-14):1748-62.
doi: 10.1016/j.addr.2013.08.004. Epub 2013 Aug 23.

Nanopreparations to overcome multidrug resistance in cancer

Niravkumar R Patel  1 , Bhushan S Pattni, Abraham H Abouzeid, Vladimir P Torchilin
Affiliations
Review

Nanopreparations to overcome multidrug resistance in cancer

Niravkumar R Patel et al. Adv Drug Deliv Rev. 2013 Nov.

Abstract

Multidrug resistance is the most widely exploited phenomenon by which cancer eludes chemotherapy. Broad variety of factors, ranging from the cellular ones, such as over-expression of efflux transporters, defective apoptotic machineries, and altered molecular targets, to the physiological factors such as higher interstitial fluid pressure, low extracellular pH, and formation of irregular tumor vasculature are responsible for multidrug resistance. A combination of various undesirable factors associated with biological surroundings together with poor solubility and instability of many potential therapeutic small & large molecules within the biological systems and systemic toxicity of chemotherapeutic agents has necessitated the need for nano-preparations to optimize drug delivery. The physiology of solid tumors presents numerous challenges for successful therapy. However, it also offers unique opportunities for the use of nanotechnology. Nanoparticles, up to 400 nm in size, have shown great promise for carrying, protecting and delivering potential therapeutic molecules with diverse physiological properties. In this review, various factors responsible for the MDR and the use of nanotechnology to overcome the MDR, the use of spheroid culture as well as the current technique of producing microtumor tissues in vitro are discussed in detail.

Keywords: Combination therapy; Multidrug resistance; Nanopreparations; Spheroid culture.

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Figures

Figure 1
Figure 1
Cellular factors responsible for the multidrug resistance.
Figure 2
Figure 2
Physiological factors responsible for the multidrug resistance and their inter-relation.
Figure 3
Figure 3
Enhanced permeability and retention effect. Due to the presence of leaky vasculature in tumor microenvironment and poor lymphatic drainage, EPR effect is observed for nanopreparations with size distribution up to 400 nm.
Figure 4
Figure 4
Rh123 uptake study in SKOV-3 and SKOV-3TR cells. The cells were treated with free tariquidar (XR9576) and tariquidar (XR) liposomes and then incubated with Rh123. FACS analysis showed that the tariquidar retained its activity when in liposomes and effectively inhibited P-gp as shown by enhanced Rh123 intensity. Reproduced with permissions from the authors.
Figure 5
Figure 5
IC50 for paclitaxel in SKOV-3 and SKOV-3TR cells. Cells were treated with paclitaxel (PCL), PCL liposomes and tariquidar (XR)-PCL combination liposomes at various concentrations. Error bars indicate mean ± S.D. *p < 0.05. Y-axis is shown in logarithmic scale. IC50 for the combination treatment was reduced as compared to PCL alone. Reproduced with permissions from the authors.
Figure 6
Figure 6
Z-Stack images of NCI-ADR-RES spheroids by confocal microscopy to study penetration of doxorubicin-loaded micelles. Treatments carried out: (a) HEPES, (b) free doxorubicin, (c) micellar doxorubicin, (d) IgG targeted micellar doxorubicin, (e) 2C5 targeted micellar doxorubicin. Reproduced with permissions from the authors.
See this image and copyright information in PMC

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