Influence of vitamin E TPGS poly(ethylene glycol) chain length on apical efflux transporters in Caco-2 cell monolayers

Collnot, Eva-Maria; Baldes, Christiane; Wempe, Michael F.; Hyatt, John A.; Navarro, Lisa; Edgar, Kevin J.; Schaefer, Ulrich F.; Lehr, Claus‐Michael

doi:10.1016/j.jconrel.2005.11.005

Cited by 170 publications

(123 citation statements)

References 38 publications

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“…It has been proposed that nonionic surfactants inhibit/modulate P-gp by various mechanisms, including changing membrane fluidity, inhibiting P-gp ATPase activity, and depleting ATP stores. [36][37][38][39][40] Interestingly, as we have previously demonstrated, if PCL5 is not maintained above an inhibitory concentration, PTX rapidly effluxes from the MDCKII-MDR1 cells, resulting in reduced inhibition of cell proliferation. 20 An additional experiment was conducted to determine the IC 50 of PTX-loaded nanospheres or micelles in the presence of PCL5 at its most effective concentration (0.05%).…”

Section: Cytotoxicity Of Ptx-loaded Nanoparticlesmentioning

confidence: 67%

The combined use of paclitaxel-loaded nanoparticles with a low-molecular-weight copolymer inhibitor of P-glycoprotein to overcome drug resistance

Wan¹,

Letchford²,

Jackson³

et al. 2013

IJN

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Two types of nanoparticles were prepared using the diblock copolymer methoxy poly(ethylene glycol)-block-poly(caprolactone) (MePEG-b-PCL), with either a short PCL block length, which forms micelles, or with a longer PCL block length, which forms kinetically "frozen core" structures termed nanospheres. Paclitaxel (PTX)-loaded micelles and nanospheres were evaluated for their cytotoxicity, cellular polymer uptake, and drug accumulation in drug-sensitive (Madin-Darby Canine Kidney [MDCK]II) and multidrug-resistant (MDR) P-glycoprotein (P-gp)-overexpressing (MDCKII-MDR1) cell lines. Both types of PTX-loaded nanoparticles were equally effective at inhibiting proliferation of MDCKII cells, but PTX-loaded micelles were more cytotoxic than nanospheres in MDCKII-MDR1 cells. The intracellular accumulation of both PTX and the diblock copolymers were similar for both nanoparticles, suggesting that the difference in cytotoxicity might be due to the different drug-release profiles. Furthermore, the cytotoxicity of these PTX-loaded nanoparticles was enhanced when these systems were subsequently or concurrently combined with a low-molecular-weight MePEG-b-PCL diblock copolymer, which we have previously demonstrated to be an effective P-gp inhibitor. These results suggest that the dual functionality of MePEG-b-PCL might be useful in delivering drug intracellularly and in modulating P-gp in order to optimize the cytotoxicity of PTX in multidrug-resistant cells.

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Section: Cytotoxicity Of Ptx-loaded Nanoparticlesmentioning

confidence: 67%

The combined use of paclitaxel-loaded nanoparticles with a low-molecular-weight copolymer inhibitor of P-glycoprotein to overcome drug resistance

Wan¹,

Letchford²,

Jackson³

et al. 2013

IJN

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show abstract

“…22,23 It has been suggested that the digested lipids and BS components enhances drug permeation by: (a) Increasing the intestinal membrane fluidity (b) Disrupting the integrity of the tight junctions (ii) The inhibitory effects of various lipid and surfactant excipients on the intestinal P-gp efflux and CYP3A metabolizing systems, which eventually leads to an enhanced drug bioavailability.…”

Section: Impact On Drug Deliverymentioning

confidence: 99%

Formulation and Evaluation of Silica Lipid Hybrid Microparticles Containing Furosemide

Kumar¹,

Habeeb²,

Mangalarapu³

et al. 2015

Int. Res. J. Pharm.

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The study of the silica-lipid hybrid (SLH) microparticles is to enhance bioavailability and efficacy of poorly water-soluble drugs after oral administration. Lipid-based delivery systems recognized as a potential strategy for improving the oral absorption. Clinical applications of any lipid-based formulations are limited by the lack of clear guidelines of incomplete understanding of absorption mechanism and invitro, invivo formulation performance. Withstanding these problems, the availability of 2-4% oral lipid based products in the pharmaceutical market worldwide has supported in addressing low bioavailability of poorly soluble drugs. A novel silica-lipid hybrid microparticulate system is used for enhancing the oral absorption of low solubility and low permeability of (BCS Class IV) drugs, that has been developed for the drug, furosemide. It describes the systematic invitro characterization of dissolution and lipolysis properties. Silica-lipid hybrid microparticles include the drug solubilizing effect of dispersed lipids and stabilizing effect of hydrophilic silica particles to increase drug solubilization, which leads to enhanced oral bioavailability. Furosemide is mainly used in the treatment of hypertension and congestive heart failure. The role of lipids and hydrophilic silica based carrier highlighted in enhancing solubility and permeability, and hence the oral bioavailability of poorly soluble drugs. The formulation composed of poorly soluble drug (furosemide) and dispersion of oil phase (Soya bean oil) in lecithin (Phospholipoid 90H), surfactant and vortexed until no crystals of drug is observed and are subsequently adsorbed by Aerosol 380 (hydrophilic fumed silica) and stabilized after being transformed to powder state. Saturation solubility studies were performed in different oils and surfactants with increased concentration of drug revealed increased solubility of furosemide. In vitro dissolution studies conducted under stimulated gastric medium revealed 2-4 fold increase in dissolution efficiencies for furosemide formulated as SLH microparticles, when compared to that of pure drug (furosemide) and a marketed formulation. Ex vivo studies showed enhanced lipid digestibility, which improved drug permeability. Solid-state characterization of SLH microparticles by XRPD (X-ray powder diffraction) and FTIR (Fourier transform infrared spectroscopy) analysis confirmed non-crystalline nature and less compatibility of furosemide in silica-lipid hybrid microparticles.

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“…Another component in PMs, namely, TPGS 1000 , is one of the membrane efflux transporters and has inhibiting functions against the adenosine triphosphate (ATP)-dependent pump P-glycoprotein (P-gp). [27][28][29] In addition to its application in enhanced chemotherapy, TPGS has recently been used as a component to modify solid-lipid nanoparticles for overcoming P-gp-mediated MDR related to leukemia. 30 In these applications, TPGS 1000 has shown certain ability to inhibit the exocytosis of the internalized nanoparticles from cancer cells.…”

mentioning

confidence: 99%

“…30 In these applications, TPGS 1000 has shown certain ability to inhibit the exocytosis of the internalized nanoparticles from cancer cells. [27][28][29][30] Therefore, it would be possible to help DOX to circumvent the MDRassociated pathways in some cancer cells while enhancing the anticancer efficacy of DOX if the carriers used for the delivery of DOX could be built using DSPE-PEG 2000 and TPGS 1000 .…”

mentioning

confidence: 99%

Nanomicelles loaded with doxorubicin and curcumin for alleviating multidrug resistance in lung cancer

Gu¹,

Li²,

Yang³

et al. 2016

IJN

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Influence of vitamin E TPGS poly(ethylene glycol) chain length on apical efflux transporters in Caco-2 cell monolayers

Cited by 170 publications

References 38 publications

The combined use of paclitaxel-loaded nanoparticles with a low-molecular-weight copolymer inhibitor of P-glycoprotein to overcome drug resistance

The combined use of paclitaxel-loaded nanoparticles with a low-molecular-weight copolymer inhibitor of P-glycoprotein to overcome drug resistance

Formulation and Evaluation of Silica Lipid Hybrid Microparticles Containing Furosemide

Nanomicelles loaded with doxorubicin and curcumin for alleviating multidrug resistance in lung cancer

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