Hyaluronic acid-coated nanoemulsions loaded with a hydrophobic ion pair of all-trans retinoic acid for improving the anticancer activity
All-trans retinoic acid (ATRA) has been studied for the treatment of cancer, including leukemia and breast cancer. This work aims to develop nanoemulsions (NE) loaded with a hydrophobic ion pair (HIP) of all-trans retinoic acid (ATRA) and a lipophilic amine, stearylamine (SA), and coated with hyalur...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Universidade de São Paulo
2019-04-01
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| Series: | Brazilian Journal of Pharmaceutical Sciences |
| Subjects: | |
| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1984-82502018000400616&lng=en&tlng=en |
| _version_ | 1818357501370826752 |
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| author | Letícia Márcia da Silva Tinoco Flávia Lidiane Oliveira da Silva Lucas Antônio Miranda Ferreira Elaine Amaral Leite Guilherme Carneiro |
| author_facet | Letícia Márcia da Silva Tinoco Flávia Lidiane Oliveira da Silva Lucas Antônio Miranda Ferreira Elaine Amaral Leite Guilherme Carneiro |
| author_sort | Letícia Márcia da Silva Tinoco |
| collection | DOAJ |
| description | All-trans retinoic acid (ATRA) has been studied for the treatment of cancer, including leukemia and breast cancer. This work aims to develop nanoemulsions (NE) loaded with a hydrophobic ion pair (HIP) of all-trans retinoic acid (ATRA) and a lipophilic amine, stearylamine (SA), and coated with hyaluronic acid (HA) to enhance anticancer activity and reducing toxicity. Blank NE was prepared by spontaneous emulsification and optimized prior to HIP incorporation. NE-ATRA was electrostatically coated with different concentrations of HA. Incorporation of ATRA-SA led to monodisperse NE with small size (129 ± 2 nm; IP 0.18 ± 0.005) and positive zeta potential (35.7 ± 1.0 mV). After coating with 0.5 mg/mL HA solution, the mean diameter slightly increased to 158 ± 5 nm and zeta potential became negative (-19.7 ± 1.2 mV). As expected, high encapsulation efficiency (near 100%) was obtained, confirmed by polarized light microscopy and infrared analysis. Formulations remained stable over 60 days and release of ATRA from NE was delayed after the hydrophilic HA-coating. HA-coated NE-ATRA was more cytotoxic than free ATRA for MDA-MB-231 and MCF-7 breast cancer cell lines, especially in the CD44 overexpressing cells. Blank coated formulations showed no cytotoxicity. These findings suggest that this easily-made HA-coated NE-ATRA formulation is a promising alternative for parenteral administration, thus improving the breast cancer therapy with this drug. |
| first_indexed | 2024-12-13T20:14:07Z |
| format | Article |
| id | doaj.art-b2bafde2e8294f149dada03934d7f106 |
| institution | Directory Open Access Journal |
| issn | 2175-9790 |
| language | English |
| last_indexed | 2024-12-13T20:14:07Z |
| publishDate | 2019-04-01 |
| publisher | Universidade de São Paulo |
| record_format | Article |
| series | Brazilian Journal of Pharmaceutical Sciences |
| spelling | doaj.art-b2bafde2e8294f149dada03934d7f1062022-12-21T23:32:51ZengUniversidade de São PauloBrazilian Journal of Pharmaceutical Sciences2175-97902019-04-0154410.1590/s2175-97902018000417361S1984-82502018000400616Hyaluronic acid-coated nanoemulsions loaded with a hydrophobic ion pair of all-trans retinoic acid for improving the anticancer activityLetícia Márcia da Silva TinocoFlávia Lidiane Oliveira da SilvaLucas Antônio Miranda FerreiraElaine Amaral LeiteGuilherme CarneiroAll-trans retinoic acid (ATRA) has been studied for the treatment of cancer, including leukemia and breast cancer. This work aims to develop nanoemulsions (NE) loaded with a hydrophobic ion pair (HIP) of all-trans retinoic acid (ATRA) and a lipophilic amine, stearylamine (SA), and coated with hyaluronic acid (HA) to enhance anticancer activity and reducing toxicity. Blank NE was prepared by spontaneous emulsification and optimized prior to HIP incorporation. NE-ATRA was electrostatically coated with different concentrations of HA. Incorporation of ATRA-SA led to monodisperse NE with small size (129 ± 2 nm; IP 0.18 ± 0.005) and positive zeta potential (35.7 ± 1.0 mV). After coating with 0.5 mg/mL HA solution, the mean diameter slightly increased to 158 ± 5 nm and zeta potential became negative (-19.7 ± 1.2 mV). As expected, high encapsulation efficiency (near 100%) was obtained, confirmed by polarized light microscopy and infrared analysis. Formulations remained stable over 60 days and release of ATRA from NE was delayed after the hydrophilic HA-coating. HA-coated NE-ATRA was more cytotoxic than free ATRA for MDA-MB-231 and MCF-7 breast cancer cell lines, especially in the CD44 overexpressing cells. Blank coated formulations showed no cytotoxicity. These findings suggest that this easily-made HA-coated NE-ATRA formulation is a promising alternative for parenteral administration, thus improving the breast cancer therapy with this drug.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1984-82502018000400616&lng=en&tlng=enAll-trans-retinoic acidBreast neoplasms.Drug deliveryHyaluronic acidNanoemulsion |
| spellingShingle | Letícia Márcia da Silva Tinoco Flávia Lidiane Oliveira da Silva Lucas Antônio Miranda Ferreira Elaine Amaral Leite Guilherme Carneiro Hyaluronic acid-coated nanoemulsions loaded with a hydrophobic ion pair of all-trans retinoic acid for improving the anticancer activity Brazilian Journal of Pharmaceutical Sciences All-trans-retinoic acid Breast neoplasms.Drug delivery Hyaluronic acid Nanoemulsion |
| title | Hyaluronic acid-coated nanoemulsions loaded with a hydrophobic ion pair of all-trans retinoic acid for improving the anticancer activity |
| title_full | Hyaluronic acid-coated nanoemulsions loaded with a hydrophobic ion pair of all-trans retinoic acid for improving the anticancer activity |
| title_fullStr | Hyaluronic acid-coated nanoemulsions loaded with a hydrophobic ion pair of all-trans retinoic acid for improving the anticancer activity |
| title_full_unstemmed | Hyaluronic acid-coated nanoemulsions loaded with a hydrophobic ion pair of all-trans retinoic acid for improving the anticancer activity |
| title_short | Hyaluronic acid-coated nanoemulsions loaded with a hydrophobic ion pair of all-trans retinoic acid for improving the anticancer activity |
| title_sort | hyaluronic acid coated nanoemulsions loaded with a hydrophobic ion pair of all trans retinoic acid for improving the anticancer activity |
| topic | All-trans-retinoic acid Breast neoplasms.Drug delivery Hyaluronic acid Nanoemulsion |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1984-82502018000400616&lng=en&tlng=en |
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