Back to Journals » International Journal of Nanomedicine » Volume 7

Formation of ion pairing as an alternative to improve encapsulation and anticancer activity of all-trans retinoic acid loaded in solid lipid nanoparticles

Authors Carneiro G, Silva, Pacheco, Souza-Fagundes, Correa N, Goes A, Oliveira, Ferreira L

Received 9 October 2012

Accepted for publication 13 November 2012

Published 12 December 2012 Volume 2012:7 Pages 6011—6020


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Guilherme Carneiro,1 Elton Luiz Silva,1 Layssa Alves Pacheco,1 Elaine Maria de Souza-Fagundes,2 Natássia Caroline Resende Corrêa,3 Alfredo Miranda de Goes,3 Mônica Cristina de Oliveira,1 Lucas Antônio Miranda Ferreira1

1Department of Pharmaceutics, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Brazil; 2Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil; 3Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil

Abstract: This work aims to develop solid lipid nanoparticles (SLNs) loaded with retinoic acid (RA) to evaluate the influence of two lipophilic amines, stearylamine (SA) and benethamine (BA), and one hydrophilic, triethylamine (TA), on drug-encapsulation efficiency (EE) and cytotoxicity in cancer cell lines. The SLNs were characterized for EE, size, and zeta potential. The mean particle size decreased from 155 ± 1 nm (SLNs without amine) to 104 ± 4, 95 ± 1, and 96 ± 1 nm for SLNs prepared with SA, BA, and TA, respectively. SA-RA-loaded SLNs resulted in positively charged particles, whereas those with TA and BA were negatively charged. The EEs were significantly improved with the addition of the amines, and they increased from 36% ± 6% (without amine) to 97% ± 2%, 90% ± 2%, and 100% ± 1% for SA, TA, and BA, respectively. However, stability studies showed higher EE for BA-RA-loaded SLNs than TA-RA-loaded SLNs after 30 days. The formulations containing SA loaded or unloaded (blank SLNs) with RA were cytotoxic in normal and cancer cell lines. In contrast, the blank SLNs containing TA or BA did not show cytotoxicity in human breast adenocarcinoma cells (MCF-7), while RA-loaded SLNs with the respective amines were significantly more cytotoxic than free RA. Furthermore, the cytotoxicity of BA-RA-loaded SLNs was significantly higher than TA-RA-loaded SLNs. These findings are in agreement with the data obtained in the evaluation of subdiploid DNA content and cell-cycle analysis, which showed better anticancer activity for BA-RA-loaded SLNs than TA-RA-loaded SLNs and free RA. Taken together, these findings suggest that the BA-RA-loaded SLN formulation is a promising alternative for the intravenous administration of RA in the treatment of cancer.

Keywords: solid lipid nanoparticles, all-trans retinoic acid, cancer, treatment, antitumor activity, ion pairing

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at 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]


Readers of this article also read:

In vivo and in vitro investigations of a nanostructured coating material – a preclinical study

Adam M, Ganz C, Xu W, Sarajian HR, Götz W, Gerber T

International Journal of Nanomedicine 2014, 9:975-984

Published Date: 14 February 2014

Degradation and osteogenic potential of a novel poly(lactic acid)/nano-sized β-tricalcium phosphate scaffold

Cao L, Duan PG, Wang HR, Li XL, Yuan FL, Fan ZY, Li SM, Dong J

International Journal of Nanomedicine 2012, 7:5881-5888

Published Date: 28 November 2012

Bioreducible and acid-labile poly(amido amine)s for efficient gene delivery

Yu ZQ, Yan JJ, You YZ, Zhou QH

International Journal of Nanomedicine 2012, 7:5819-5832

Published Date: 23 November 2012

Do calcifying nanoparticles really contain 16S rDNA?

Shiekh FA

International Journal of Nanomedicine 2012, 7:5051-5052

Published Date: 18 September 2012

Fabrication and characterization of a rapid prototyped tissue engineering scaffold with embedded multicomponent matrix for controlled drug release

Chen M, Le DQ, Hein S, Li P, Nygaard JV, Kassem M, Kjems J, Besenbacher F, Bünger C

International Journal of Nanomedicine 2012, 7:4285-4297

Published Date: 3 August 2012

Evaluation of the genotoxicity of cellulose nanofibers

de Lima R, Feitosa LO, Maruyama CR, Barga MA, Yamawaki PC, Vieira IJ, Teixeira EM, Corrêa AC, Mattoso LH, Fraceto LF

International Journal of Nanomedicine 2012, 7:3555-3565

Published Date: 11 July 2012

A novel lipid-based nanomicelle of docetaxel: evaluation of antitumor activity and biodistribution

Ma M, Hao Y, Liu N, Yin Z, Wang L, Liang X, Zhang X

International Journal of Nanomedicine 2012, 7:3389-3398

Published Date: 4 July 2012

Engineered hepatitis B virus surface antigen L protein particles for in vivo active targeting of splenic dendritic cells

Matsuo H, Yoshimoto N, Iijima M, Niimi T, Jung J, Jeong SY, Choi EK, Sewaki T, Arakawa T, Kuroda S

International Journal of Nanomedicine 2012, 7:3341-3350

Published Date: 3 July 2012

Practical preparation procedures for docetaxel-loaded nanoparticles using polylactic acid-co-glycolic acid

Keum CG, Noh YW, Baek JS, Lim JH, Hwang CJ, Na YG, Shin SC, Cho CW

International Journal of Nanomedicine 2011, 6:2225-2234

Published Date: 7 October 2011