Effect of stealthy liposomal topotecan plus amlodipine on the multidrug‐resistant leukaemia cells <i>in vitro</i> and xenograft in mice

Li, X.; Lu, Wei; Liang, Gong-Wen; Ruan, Guo‐Rui; Hong, Haiyan; Long, Chengnian; Zhang, Y. T.; Liu, Y.; Wang, J. C.; Zhang, X.; Zhang, Q.

doi:10.1111/j.1365-2362.2006.01643.x

Cited by 29 publications

(13 citation statements)

References 29 publications

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“…Due to this activity, targeted delivery of AD in liposomal preparations, either alone or in combination with other drugs, has been employed by various workers with significant success [124, 125, 129]. …”

Section: Formulations Of Admentioning

confidence: 99%

Formulations of Amlodipine: A Review

Sheraz

Ahsan

Khan

et al. 2016

Journal of Pharmaceutics

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Amlodipine (AD) is a calcium channel blocker that is mainly used in the treatment of hypertension and angina. However, latest findings have revealed that its efficacy is not only limited to the treatment of cardiovascular diseases as it has shown to possess antioxidant activity and plays an important role in apoptosis. Therefore, it is also employed in the treatment of cerebrovascular stroke, neurodegenerative diseases, leukemia, breast cancer, and so forth either alone or in combination with other drugs. AD is a photosensitive drug and requires protection from light. A number of workers have tried to formulate various conventional and nonconventional dosage forms of AD. This review highlights all the formulations that have been developed to achieve maximum stability with the desired therapeutic action for the delivery of AD such as fast dissolving tablets, floating tablets, layered tablets, single-pill combinations, capsules, oral and transdermal films, suspensions, emulsions, mucoadhesive microspheres, gels, transdermal patches, and liposomal formulations.

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Section: Formulations Of Admentioning

confidence: 99%

Formulations of Amlodipine: A Review

Sheraz

Ahsan

Khan

et al. 2016

Journal of Pharmaceutics

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“…This is illustrated by the following two studies. For the combination of topotecan and amlodipine, the co-encapsulated liposome formulation has been studied in MDR human chronic myelogenous leukemia in vitro and in vivo [125]. Amlodipine not only reversed the resistance of topotecan in MDR HL-60 leukemia cells but also enhanced the apoptosisinducing effect of topotecan through caspases 3, 7 and 8 in vitro.…”

Section: Combinations With Inhibitors Of P-glycoproteinmentioning

confidence: 99%

Lipid-Based Nanoparticulate Systems for the Delivery of Anti-Cancer Drug Cocktails: Implications on Pharmacokinetics and Drug Toxicities

Chiu¹,

Wong²,

Ling³

et al. 2009

CDM

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The use of drug cocktails has become a widely adopted strategy in clinical cancer therapy. Cytotoxic drug cocktails are often administered based on maximum tolerated dose (MTD) of each agent, with the belief of achieving maximum cell kill through tolerable toxicity level. Yet, MTD administration may not have fully captured the therapeutic synergism that exists among the individual agents in the drug cocktail, as the response to a cocktail regimen, that is, whether the effect is synergistic or not, could be highly sensitive to the concentration ratios of the individual drugs at the site of action. It is important to realize that the inherently different pharmacokinetic profiles of the individual agents could have significant influence on the response to an anti-cancer drug cocktail by dictating the amount of the individual agents reaching the tumor site and therefore the concentration ratios. Furthermore, the individual agents may have unfavorable pharmacokinetic interactions that add to the difficulty in determining the therapeutic and/or toxicological effects of the drug cocktail. In this review, we will focus on how lipid-based nanoparticulate systems could address the above issues associated with anti-cancer drug cocktails. Specifically, we will highlight the use of liposome systems as the means to control and coordinate the delivery of various anti-cancer drug cocktails, encompassing conventional chemotherapeutics, chemosensitizing agents and molecularly targeted agents.

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“…About the other compounds, in general, they have not reached the experimentation in clinical trials. Presently only amlodipine, associated and delivered together topotecan by stealthy liposomes [20,21] seems to possess interesting characteristics in preclinical studies, thus having some objective chances to overcome the MDR phenomena. Nevertheless, also in this case it is not possible to foresee the possible toxicity of this in humans, since this drug is also a potent Ca ++ antagonist and might therefore display potential cardiovascular doselimiting toxicities.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of MDR1 activity and induction of apoptosis by analogues of nifedipine and diltiazem: an in vitro analysis

et al. 2009

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We report herein the reversal of multidrug resistance-1 (MDR1) in A2780/DX3 cells by the two nifedipine-like compounds 1 and 2 that are part of a library of 1,4-dihydropyridines (1,4-DHPs) calcium-channel modulators bearing in C-4 a different substituted imidazo[2,1-b]thiazole system. By methylthiazol tetrazolium (MTT) assay, cytofluorimetry, and fluorescence microscopy we evaluated their ability to reverse MDR in our cell system. Moreover, together with compound 3 (the diltiazem-like 8-(4-chlorophenyl)-5-methyl-8-[(2Z)-pent-2-en-1-yloxy]-8H-[1,2,4]oxadiazolo[3,4-c][1,4]thiazin-3-one) we analyzed their ability to potentiate the triggering of apoptosis after exposure to doxorubicin, through the nuclear morphological analysis after 4',6-diamidino-2-phenylindole (DAPI), the fluorescein isothiocyanate (FITC)-Annexin-V/propidium iodide (PI) staining and the caspase activity determination. Our results demonstrate that compounds 1 and 2, at concentrations showing a very low (5%) or absent inhibition of cell proliferation, in combination with doxorubicin enhance its antiproliferative activity (from 30% to 54% IC(50) reduction) in A2780/DX3 cells through an increase of doxorubicin intracellular accumulation. These compounds together with compound 3, which has already been demonstrated to act as a potent inhibitor of MDR1 function, were also able to significantly potentiate the activation of the apoptosis machinery triggered by the exposure to doxorubicin. In conclusion, our results identify two new molecules structurally related to the calcium-channel blocker nifedipine, but characterized by a very low LTCC blockers activity, able to potentiate the antiproliferative and apoptotic activities of doxorubicin through an increase of its intracellular concentration likely caused by the inhibition of MDR1 function.

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Effect of stealthy liposomal topotecan plus amlodipine on the multidrug‐resistant leukaemia cells in vitro and xenograft in mice

Cited by 29 publications

References 29 publications

Formulations of Amlodipine: A Review

Formulations of Amlodipine: A Review

Lipid-Based Nanoparticulate Systems for the Delivery of Anti-Cancer Drug Cocktails: Implications on Pharmacokinetics and Drug Toxicities

Inhibition of MDR1 activity and induction of apoptosis by analogues of nifedipine and diltiazem: an in vitro analysis

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