Resistance modulation in CHO cells by R-verapamil and bile salts is associated with physical and chemical changes in the cell membrane

Jh, Dolderer; Zimmer, Guido; Bg, Woodcock; Bockhorn, H.; Bickeböller, Ralf; Schuldes, H.

doi:10.5414/cpp38196

Cited by 14 publications

(7 citation statements)

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“…139 Furthermore, multidrugresistant Chinese hamster ovary cells were shown to exhibit lower membrane fluidity than did their drug-sensitive counterpart. 140 In contrast, membrane fluidity was found to increase in the presence of ether, benzyl alcohol, Tween 20, Triton X-100, and verapmil, and this increase in fluidity was correlated with the inhibition of P-gp ATPase activity in multidrug-resistant hamster ovary cells. 141 Moreover, the bile salt, taurochenodeoxycholate, and verapamil increased membrane fluidity and decreased P-gp activity in multidrug-resistant hamster ovary cells.…”

Section: Atp-binding Cassette Transporter Proteinsmentioning

confidence: 93%

A Mechanistic Approach to Understanding the Factors Affecting Drug Absorption: A Review of Fundamentals

Martinez¹,

Amidon²

2002

The Journal of Clinical Pharma

545

315

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This article provides an overview of the patient-specific and drug-specific variables that can affect drug absorption following oral product administration. The oral absorption of any chemical entity reflects a complex spectrum of events. Factors influencing product bioavailability include drug solubility, permeability, and the rate of in vivo dissolution. In this regard, the Biopharmaceutics Classification System has proven to be an important tool for predicting compounds likely to be associated with bioavailability problems. It also helps in identifying those factors that may alter the rate and extent of drug absorption. Product bioavailability can also be markedly influenced by patient attributes such as the integrity of the gastrointestinal tract, physiological status, site of drug absorption, membrane transporters, presystemic drug metabolism (intrinsic variables), and extrinsic variables such as the effect of food or concomitant medication. Through an awareness of a drug's physicochemical properties and the physiological processes affecting drug absorption, the skilled pharmaceutical scientist can develop formulations that will maximize product availability. By appreciating the potential impact of patient physiological status, phenotype, age, gender, and lifestyle, dosing regimens can be tailored to better meet the needs of the individual patient.

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Section: Atp-binding Cassette Transporter Proteinsmentioning

confidence: 93%

A Mechanistic Approach to Understanding the Factors Affecting Drug Absorption: A Review of Fundamentals

Martinez¹,

Amidon²

2002

The Journal of Clinical Pharma

545

315

View full text Add to dashboard Cite

show abstract

“…Ultrasound could alter the membrane lipid arrangement, increasing membrane fluidity that could facilitate drug transport to overcome drug resistance [122]. Similarly, as a means of chemical methods, R-verapamil and linolenic acid have been shown to reverse drug resistance in human bladder carcinoma cell lines by modifying the membrane fluidity [123, 124]. Due to lipophilic nature, R-verapamil can accumulates in the hydrophobic region, the steric effects of isopropyl sides chain seem to reduces the van der Waals forces between lipid molecules, resulting in more fluid membranes.…”

Section: Strategies To Improve Np-based Drug Delivery To Overcome mentioning

confidence: 99%

Biophysics of cell membrane lipids in cancer drug resistance: Implications for drug transport and drug delivery with nanoparticles

Peetla

Vijayaraghavalu

Labhasetwar

2013

Advanced Drug Delivery Reviews

235

214

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In this review, we focus on the biophysics of cell membrane lipids, particularly when cancers develop acquired drug resistance, and how biophysical changes in resistant cell membrane influence drug transport and nanoparticle-mediated drug delivery. Recent advances in membrane lipid research show the varied roles of lipids in regulating membrane P-glycoprotein function, membrane trafficking, apoptotic pathways, drug transport, and endocytic functions, particularly endocytosis, the primary mechanism of cellular uptake of nanoparticle-based drug delivery systems. Since acquired drug resistance alters lipid biosynthesis, understanding the role of lipids in cell membrane biophysics and its effect on drug transport is critical for developing effective therapeutic and drug delivery approaches to overcoming drug resistance. Here we discuss novel strategies for (a) modulating the biophysical properties of membrane lipids of resistant cells to facilitate drug transport and regain endocytic function and (b) developing effective nanoparticles based on their biophysical interactions with membrane lipids to enhance drug delivery and overcome drug resistance.

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“…The ability of Pluronic copolymer, one poly (ethylene oxide) block copolymer, to antagonize P-gp and sensitize MDR cells appears to be a result of ATP depletion, and inhibition of P-gp and MRP drug efflux proteins [41]. Studies with MDR modifiers such as bile salts indicated that perturbations of the cell membrane structure may influence P-gp-mediated drug transport [33,42,43]. These modifiers may influence cytotoxic drug action by producing structural changes to the lipid domains in the plasma membrane.…”

Section: The Effect Of Excipients On Efflux Transportmentioning

confidence: 99%

Self-Emulsifying Drug Delivery Systems: Strategy for Improving Oral Delivery of Poorly Soluble Drugs

Tang¹,

Sun²,

Zhang

2007

CDTH

150

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Drugs are most often administered by the oral route. However, more than 40% of new chemical entities exhibit poor aqueous solubility, resulting in unsatisfactory oral drug delivery. Recently, much attention has been focused on selfemulsifying drug delivery systems (SEDDS) to improve the oral bioavailability of poorly aqueous soluble drugs. SEDDS are isotropic mixtures of oil, surfactants, solvents and co-solvents/surfactants. The principal characteristic of these systems is their ability to form fine oil-in-water (o/w) emulsions or microemulsions upon mild agitation following dilution by an aqueous phase. For lipophilic drugs, which display dissolution rate-limited absorption, SEDDS may be a promising strategy to improve the rate and extent of oral absorption. This article gives an overview of the new excipients used in SEDDS and biopharmaceutical aspects of SEDDS. The application of SEDDS and closely related lipid-based systems as drug delivery vehicles is also introduced, with particular emphasis being placed on the application of SEDDS in traditional Chinese medicine (TCM).

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Resistance modulation in CHO cells by R-verapamil and bile salts is associated with physical and chemical changes in the cell membrane

Cited by 14 publications

References 0 publications

A Mechanistic Approach to Understanding the Factors Affecting Drug Absorption: A Review of Fundamentals

A Mechanistic Approach to Understanding the Factors Affecting Drug Absorption: A Review of Fundamentals

Biophysics of cell membrane lipids in cancer drug resistance: Implications for drug transport and drug delivery with nanoparticles

Self-Emulsifying Drug Delivery Systems: Strategy for Improving Oral Delivery of Poorly Soluble Drugs

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