Back to Browse Journals » International Journal of Nanomedicine » Volume 3 » Issue 4

New methodologies to characterize the effectiveness of the gene transfer mediated by DNA-chitosan nanoparticles

Authors Miguel N Centelles, Cheng Qian, Miguel A Campanero, Juan M Irache

Published Date October 2008 Volume 2008:3(4) Pages 451—460

DOI http://dx.doi.org/10.2147/IJN.S3445

Published 7 October 2008

Miguel N Centelles1, Cheng Qian2, Miguel A Campanero1, Juan M Irache1

1Centro Galénico, Departamento Farmacia y Tecnología Farmacéutica, University of Navarra, Irunlarrea 1, 31080, Pamplona, Spain; 2Centro de Investigación Medica Aplicada (CIMA), Facultad de Medicina, Gene Therapy Unit, University of Navarra, 31008 Pamplona, Spain

Abstract: In this work three DNA-chitosan nanoparticle formulations (Np), differing in the molecular weight (MW; 150 kDa, 400 kDa, and 600 kDa) of the polysaccharide, were prepared and administered by two different administration routes: the hydrodynamics-based procedure and the intraduodenal injection. After the hydrodynamic injection, DNA-chitosan nanoparticles were predominantly accumulated in the liver, where the transgene was expressed during at least 105 days. No significant influence of MW was observed on the levels of luciferase expression. The curves of bioluminescence versus time obtained using the charge-coupled device (CCD) camera were described and divided in three phases: (i) the initial phase, (ii) the sustained release step and (iii) the decline phase (promotor inactivation, immunological and physiological processes). From these curves, which describe the transgene expression profile, the behavior of the different formulations as gene delivery systems was characterized. Therefore, the following parameters such as Cmax (maximum level of detected bioluminescence), AUC (area under the bioluminescence-time curve) and MET (mean time of the transgene expression) were calculated. This approach offers the possibility of studying and comparing transgene expression kinetics among a wide variety of gene delivery systems. Finally, the intraduodenal administration of naked DNA permitted the gene transfer in a dose dependent manner quantifiable with the CCD camera within 3 days. Nevertheless, the same administration procedure of the three formulations did not improve the levels of transgene expression obtained with naked DNA. This fact could be explained by the rapid physiological turn-over of enterocytes and by the ability of chitosan nanoparticles to control the DNA release.

Keywords: chitosan, nanoparticles, gene delivery, hydrodynamics-based procedure, bioluminescence, intestine

Download Article [PDF] 

Creative Commons License This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution - Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php

Readers of this article also read:

Peptide ligand and PEG-mediated long-circulating liposome targeted to FGFR overexpressing tumor in vivo

Cai L, Wang X, Wang W, Qiu N, Wen J, Duan X, Li X, Chen X, Yang L, Qian Z, Wei Y, Chen L

International Journal of Nanomedicine 2012, 7:4499-4510

Published Date: 14 August 2012

Cationized dextran nanoparticle-encapsulated CXCR4-siRNA enhanced correlation between CXCR4 expression and serum alkaline phosphatase in a mouse model of colorectal cancer

Abedini F, Hosseinkhani H, Ismail M, Domb AJ, Omar AR, Chong PP, Hong PD, Yu DS, Farber IY

International Journal of Nanomedicine 2012, 7:4159-4168

Published Date: 31 July 2012

Influences of surface coatings and components of FePt nanoparticles on the suppression of glioma cell proliferation

Sun H, Chen X, Chen D, Dong M, Fu X, Li Q, Liu X, Wu Q, Qiu T, Wan T, Li S

International Journal of Nanomedicine 2012, 7:3295-3307

Published Date: 6 July 2012

Nanofiber composites containing N-heterocyclic carbene complexes with antimicrobial activity

Elzatahry AA, Al-Enizi AM, Elsayed EA, Butorac RR, Al-Deyab SS, Wadaan MAM, Cowley AH

International Journal of Nanomedicine 2012, 7:2829-2832

Published Date: 7 June 2012

Bypassing multidrug resistance in human breast cancer cells with lipid/polymer particle assemblies

Li B, Xu H, Li Z, Yao M, Xie M, Shen H, Shen S, Wang X, Jin Y

International Journal of Nanomedicine 2012, 7:187-197

Published Date: 9 January 2012

Microencapsulation of nanoemulsions: novel Trojan particles for bioactive lipid molecule delivery

Li X, Anton N, Ta TMC, Zhao M, Messaddeq N, Vandamme TF

International Journal of Nanomedicine 2011, 6:1313-1325

Published Date: 24 June 2011

Corneal abrasion

Scott Fraser

Clinical Ophthalmology 2010, 4:387-390

Published Date: 26 April 2010