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Comparative Study of Different Nano-Formulations of Curcumin for Reversal of Doxorubicin Resistance in K562R Cells

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Abstract

Purpose

Curcumin is very well established as a chemo-therapeutic, chemo-preventive and chemo-sensitizing agent in diverse disease conditions. As the isolated pure form has poor solubility and pharmacokinetic problems, therefore it is encapsulated in to several nano-formulations to improve its bioavailability. Here in the current study, we aim to compare different nano-formulations of curcumin for their chemo-sensitizing activity in doxorubicin (DOX) resistant K562 cells.

Methods

Four different curcumin formulations were prepared namely DMSO assisted curcumin nano-dispersion (CurD, 260 nm), liposomal curcumin (CurL, 165 nm), MPEG-PCL micellar curcumin (CurM, 18 nm) and cyclodextrin encapsulated curcumin (CurN, 37 nm). The formulations were subjected to particle characterizations (size, zeta potential, release studies), followed by biological assays such as cellular uptake, P-gp inhibitory activity and reversal of DOX resistance by co-treatment with DOX.

Results

Curcumin uptake in K562N and K562R cells was mildly reduced when treated with CurL and CurM, while for CurD and CurN the uptake remained equivalent. However, CurL retained P-gp inhibitory activity of curcumin and with a considerable chemo-sensitizing effect but CurM showed no P-gp inhibitory activity. CurN retained above biological activities, but requires a secondary carrier under in vivo conditions.

Conclusions

From the results, CurM was found to be most suitable for solubilization of curcumin where as CurL can be considered as most suitable nano-formulation for reversal of DOX resistance.

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Abbreviations

ACN:

Acetonitrile

DCM:

Dichloromethane

DMSO:

Dimethyl sulfoxide

DOX:

Doxorubicin

DSPE-PEG:

1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[maleimide(polyethylene glycol)]

EPR:

Enhanced permeation and retention

FL-1:

Fluorescence channel-1

HP-β-CD:

Hydroxyl propyl-β-cyclodextrin

HSPC:

Hydrogenated soy phosphatidyl choline

MFI:

Mean fluorescence intensity

MPEG-P(CL-co-PDO):

Methoxypoly(ethylene glycol)-b-poly(ε-caprolactone-co-p-dioxanone)

MPEG-PCL:

Methoxypoly(ethylene glycol)-b-poly(ε-caprolactone)

OPA:

Ortho-phosphoric acid

PEO-PCL:

Polyethylene oxide-b- poly-ε-caprolactone

PFA:

P-formaldehyde

P-gp:

P-glycoprotein

PLGA:

Polylactic-glycolic acid

PMS:

Phenazine methosulfate

PVA:

Polyvinyl alcohol

TPGS:

D-α-tocopherylpolyethylene glycol

XTT:

(2,3-Bis-(2-Methoxy-4-Nitro-5-Sulfophenyl)-2H-Tetrazolium-5-Carboxanilide)

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Acknowledgments and Disclosures

Authors are thankful to Dr Soumen Chakraborty, Institute of life sciences, Bhubaneswar for providing the cell line. Authors acknowledge SERB, Govt. of India, for funding “Fast Track Scheme for Young Scientists” grant (No.SERC/LS-411/2011) and NISER, DAE, Govt. of India, for research fellowship. The authors declare that they have no conflict of interest.

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  1. School of Biological Sciences, National Institute of Science Education and Research (NISER), HBNI, PO- Bhimpur-Padanpur, Via- Jatni, Khurda, 752050, India

    Tapan K. Dash & V. Badireenath Konkimalla

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  1. Tapan K. Dash
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Correspondence to V. Badireenath Konkimalla.

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Dash, T.K., Konkimalla, V.B. Comparative Study of Different Nano-Formulations of Curcumin for Reversal of Doxorubicin Resistance in K562R Cells. Pharm Res 34, 279–289 (2017). https://doi.org/10.1007/s11095-016-2060-8

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  • DOI: https://doi.org/10.1007/s11095-016-2060-8

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