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

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....

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Autores principales: Carneiro, Guilherme, Silva, Elton Luiz, Pacheco, Layssa Alves, de Souza-Fagundes, Elaine Maria, Corrêa, Natássia Caroline Resende, de Goes, Alfredo Miranda, de Oliveira, Mônica Cristina, Ferreira, Lucas Antônio Miranda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3525049/
https://www.ncbi.nlm.nih.gov/pubmed/23251090
http://dx.doi.org/10.2147/IJN.S38953
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author Carneiro, Guilherme
Silva, Elton Luiz
Pacheco, Layssa Alves
de Souza-Fagundes, Elaine Maria
Corrêa, Natássia Caroline Resende
de Goes, Alfredo Miranda
de Oliveira, Mônica Cristina
Ferreira, Lucas Antônio Miranda
author_facet Carneiro, Guilherme
Silva, Elton Luiz
Pacheco, Layssa Alves
de Souza-Fagundes, Elaine Maria
Corrêa, Natássia Caroline Resende
de Goes, Alfredo Miranda
de Oliveira, Mônica Cristina
Ferreira, Lucas Antônio Miranda
author_sort Carneiro, Guilherme
collection PubMed
description 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.
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spelling pubmed-35250492012-12-18 Formation of ion pairing as an alternative to improve encapsulation and anticancer activity of all-trans retinoic acid loaded in solid lipid nanoparticles Carneiro, Guilherme Silva, Elton Luiz Pacheco, Layssa Alves de Souza-Fagundes, Elaine Maria Corrêa, Natássia Caroline Resende de Goes, Alfredo Miranda de Oliveira, Mônica Cristina Ferreira, Lucas Antônio Miranda Int J Nanomedicine Original Research 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. Dove Medical Press 2012 2012-12-12 /pmc/articles/PMC3525049/ /pubmed/23251090 http://dx.doi.org/10.2147/IJN.S38953 Text en © 2012 Carneiro et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.
spellingShingle Original Research
Carneiro, Guilherme
Silva, Elton Luiz
Pacheco, Layssa Alves
de Souza-Fagundes, Elaine Maria
Corrêa, Natássia Caroline Resende
de Goes, Alfredo Miranda
de Oliveira, Mônica Cristina
Ferreira, Lucas Antônio Miranda
Formation of ion pairing as an alternative to improve encapsulation and anticancer activity of all-trans retinoic acid loaded in solid lipid nanoparticles
title Formation of ion pairing as an alternative to improve encapsulation and anticancer activity of all-trans retinoic acid loaded in solid lipid nanoparticles
title_full Formation of ion pairing as an alternative to improve encapsulation and anticancer activity of all-trans retinoic acid loaded in solid lipid nanoparticles
title_fullStr Formation of ion pairing as an alternative to improve encapsulation and anticancer activity of all-trans retinoic acid loaded in solid lipid nanoparticles
title_full_unstemmed Formation of ion pairing as an alternative to improve encapsulation and anticancer activity of all-trans retinoic acid loaded in solid lipid nanoparticles
title_short Formation of ion pairing as an alternative to improve encapsulation and anticancer activity of all-trans retinoic acid loaded in solid lipid nanoparticles
title_sort formation of ion pairing as an alternative to improve encapsulation and anticancer activity of all-trans retinoic acid loaded in solid lipid nanoparticles
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3525049/
https://www.ncbi.nlm.nih.gov/pubmed/23251090
http://dx.doi.org/10.2147/IJN.S38953
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