Nanopreparations to overcome multidrug resistance in cancer

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 micro tumor tissues in vitro are discussed in detail.

pH-triggered surface charge-switchable polymer micelles for the co-delivery of paclitaxel/disulfiram and overcoming multidrug resistance in cancer

“…12,47 To overcome this drug efflux mechanism, it is necessary to either inhibit its expression, inhibit its function, or bypass transporter recognition. 48 The potential effect of DSF on the P-gp activity in MCF-7/ADR cells was investigated using Rh123 as a P-gp substrate. As shown in Figure 11C, when the concentration of Rh123 was 5, 10 and 20 μg/mL, the mean fluorescence intensity of the MCF-7 cells was 108.5-, 147.8-and 155.9-folds higher than that of MCF-7/ADR cells, respectively, which indicated that MCF-7/ADR cells retained strong MDR properties, while the MCF-7 cells were relatively sensitive.…”

The cellular uptake mechanism, intracellular transportation, and exocytosis of polyamidoamine dendrimers in multidrug-resistant breast cancer cells

“…2 Compared with other efforts, the nanocarriers can overcome the MDR by multiple approaches and attract more attention. 3,4 Nanocarriers, such as polymeric micelles, 5 liposomes, 6 nanoparticles, 7 and dendrimers, 8 are widely used to combat MDR in cancer.…”

Preparation of bufalin-loaded pluronic polyetherimide nanoparticles, cellular uptake, distribution, and effect on colorectal cancer

“…18,19 Targeting nanoparticulate drug delivery systems, especially biodegradable nanoparticles, provides opportunities to meet these existing challenges, with the advantages of improved pharmacokinetics, favored tumor accumulation, and reduced side effects. [20][21][22] Hydrophilic pluronic polymers have a novel type of amphiphilic, nonionic surfactant micelle structure that is insoluble in the aqueous solution of the compound, which provides good solubility in the hydrophobic microenvironment, thereby increasing the solubility of water-soluble substances. The potential use of pluronic polymers as biomedical drug carriers, for controlled drug release and gene therapy, has been given much attention.…”