Back to Journals » International Journal of Nanomedicine » Volume 7

Uptake and transport of a novel anticancer drug-delivery system: lactosyl-norcantharidin-associated N-trimethyl chitosan nanoparticles across intestinal Caco-2 cell monolayers

Authors

Guan M, Zhu QL, Liu Y, Bei YY, Gu ZL, Zhang XN, Zhang Q

Received 18 January 2012

Accepted for publication 11 February 2012

Published 11 April 2012 Volume 2012:7 Pages 1921—1930

DOI https://doi.org/10.2147/IJN.S30034

Review by Single-blind

Peer reviewer comments 5

Min Guan1, Qiao-Ling Zhu1, Yang Liu1, Yong-Yan Bei1, Zong-Lin Gu1, Xue-Nong Zhang1, Qiang Zhang2
1Department of Pharmaceutics, College of Pharmaceutical Science, Soochow University, Suzhou, People's Republic of China; 2Department of Pharmaceutics, School of Pharmaceutical Science, Peking University, Beijing, People's Republic of China

Abstract: In this paper, novel liver-targeting nanoparticles (NPs), lactosyl-norcantharidin (Lac-NCTD)-associated N-trimethyl chitosan (TMC) NPs (Lac-NCTD-TMC-NPs), were prepared using ionic cross-linkage. The physical properties, particle size, and encapsulation efficiency of the nanoparticles were then investigated. The continuous line of heterogeneous human epithelial colorectal adenocarcinoma cells (Caco-2) cell monolayer model was used to study the transport mechanism of Lac-NCTD, and the effects of factors such as time, temperature, pH level, drug concentration, enhancers, and inhibitors. This model was also used to indicate the differences among Lac-NCTD, Lac-NCTD-associated chitosan NPs (Lac-NCTD-CS-NPs), and Lac-NCTD-TMC-NPs in the absorption and transportation of membranes. Drug concentration levels were measured using high-performance liquid chromatography. Active transport and paracellular transport were suggested to be both the primary and secondary mechanisms for Lac-NCTD absorption, respectively. Lac-NCTD uptake and absorption were not controlled by pH levels, but were positively correlated to uptake time, and negatively correlated to temperature. The basolateral to apical apparent permeability coefficients (Papps) were higher than those of the apical to basolateral values. The inhibitor of P-glycoprotein and the multidrug resistance-associated protein 2 significantly enhanced the uptake amount of Lac-NCTD. Compared with Lac-NCTD, Lac-NCTD-CS-NPs and Lac-NCTD-TMC-NPs significantly enhanced drug absorption. Additionally, the latter exhibited stronger action. Lac-NCTD-NPs could penetrate the plasma membrane of Caco-2 cells and translocate into the cytoplasm and even into the nucleus.
Nanoparticles were uptaken into Caco-2 cells through the endocytosis pathway.

Keywords: Lac-NCTD, Lac-NCTD-TMC-NPs, Caco-2 cell, transport

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]

 

Other articles by this author:

Stepwise pH-responsive nanoparticles for enhanced cellular uptake and on-demand intracellular release of doxorubicin

Chen WL, Li F, Tang Y, Yang SD, Li JZ, Yuan ZQ, Liu Y, Zhou XF, Liu C, Zhang XN

International Journal of Nanomedicine 2017, 12:4241-4256

Published Date: 6 June 2017

Low-density lipoprotein-coupled micelles with reduction and pH dual sensitivity for intelligent co-delivery of paclitaxel and siRNA to breast tumor

Zhu WJ, Yang SD, Qu CX, Zhu QL, Chen WL, Li F, Yuan ZQ, Liu Y, You BG, Zhang XN

International Journal of Nanomedicine 2017, 12:3375-3393

Published Date: 26 April 2017

Liposomes coated with N-trimethyl chitosan to improve the absorption of harmine in vivo and in vitro

Chen WL, Yuan ZQ, Liu Y, Yang SD, Zhang CG, Li JZ, Zhu WJ, Li F, Zhou XF, Lin YM, Zhang XN

International Journal of Nanomedicine 2016, 11:325-336

Published Date: 19 January 2016

N-Succinyl-chitosan nanoparticles coupled with low-density lipoprotein for targeted osthole-loaded delivery to low-density lipoprotein receptor-rich tumors

Zhang CG, Zhu QL, Zhou Y, Liu Y, Chen WL, Yuan ZQ, Yang SD, Zhou XF, Zhu AJ, Zhang XN, Jin Y

International Journal of Nanomedicine 2014, 9:2919-2932

Published Date: 13 June 2014

Synthesis and characterization of low-toxicity N-caprinoyl-N-trimethyl chitosan as self-assembled micelles carriers for osthole

Hu XJ, Liu Y, Zhou XF, Zhu QL, Bei YY, You BG, Zhang CG, Chen WL, Wang ZL, Zhu AJ, Zhang XN, Fan YJ

International Journal of Nanomedicine 2013, 8:3543-3558

Published Date: 20 September 2013

Application of the central composite design to optimize the preparation of novel micelles of harmine

Bei YY, Zhou XF, You BG, Yuan ZQ, Chen WL, Xia P, Liu Y, Jin Y, Hu XJ, Zhu QL, Zhang CG, Zhang XN, Zhang L

International Journal of Nanomedicine 2013, 8:1795-1808

Published Date: 6 May 2013

Novel norcantharidin-loaded liver targeting chitosan nanoparticles to enhance intestinal absorption

Bei YY, Chen XY, Liu Y, Xu JY, Wang WJ, Gu ZL, Xing KL, Zhu AJ, Chen WL, Shi LS, Wang Q, Zhang XN, Zhang Q

International Journal of Nanomedicine 2012, 7:1819-1827

Published Date: 3 April 2012

Pharmacokinetics, tissue distribution, and metabolites of a polyvinylpyrrolidone-coated norcantharidin chitosan nanoparticle formulation in rats and mice, using LC-MS/MS

Ding XY, Hong CJ, Liu Y, Gu ZL, Xing KL, Zhu AJ, Chen WL, Shi LS, Zhang XN, Zhang Q

International Journal of Nanomedicine 2012, 7:1723-1735

Published Date: 2 April 2012

Readers of this article also read:

Molecular targets in arthritis and recent trends in nanotherapy

Roy K, Kanwar RK, Kanwar JR

International Journal of Nanomedicine 2015, 10:5407-5420

Published Date: 26 August 2015

Comparative efficacy and safety of local and systemic methotrexate injection in cesarean scar pregnancy

Peng P, Gui T, Liu X, Chen W, Liu Z

Therapeutics and Clinical Risk Management 2015, 11:137-142

Published Date: 27 January 2015

Is increasing the dose of Entecavir effective in partial virological responders?

Erturk A, Adnan Akdogan R, Parlak E, Cure E, Cumhur Cure M, Ozturk C

Drug Design, Development and Therapy 2014, 8:621-625

Published Date: 29 May 2014

Vincristine sulfate liposomal injection for acute lymphoblastic leukemia

Soosay Raj TA, Smith AM, Moore AS

International Journal of Nanomedicine 2013, 8:4361-4369

Published Date: 6 November 2013

Photodynamic therapy of a 2-methoxyestradiol tumor-targeting drug delivery system mediated by Asn-Gly-Arg in breast cancer

Shi J, Wang Z, Wang L, Wang H, Li L, Yu X, Zhang J, Ma R, Zhang Z

International Journal of Nanomedicine 2013, 8:1551-1562

Published Date: 19 April 2013

Controlled-release approaches towards the chemotherapy of tuberculosis

Saifullah B, Hussein MZ, Hussein Al Ali SH

International Journal of Nanomedicine 2012, 7:5451-5463

Published Date: 12 October 2012