Preclinical evaluation of L-fucoside from lapachol-loaded nanoemulsion as a strategy to breast cancer treatment
Breast cancer prevails as the most common cancer in women, underscoring an urgent need for more effective therapies. This study explores the potential of our newly developed nanoemulsion containing a novel fucoside derivative of lapachol (NE-F-LapA) as an intravenous treatment strategy. We sought to...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223018528 |
| _version_ | 1797364221364666368 |
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| author | Sued Eustaquio Mendes Miranda Janaina de Alcantara Lemos Flaviano Melo Ottoni Geovanni Dantas Cassali Danyelle M. Townsend Carolina de Aguiar Ferreira Ricardo Jose Alves Lucas Antonio Miranda Ferreira Andre Luis Branco de Barros |
| author_facet | Sued Eustaquio Mendes Miranda Janaina de Alcantara Lemos Flaviano Melo Ottoni Geovanni Dantas Cassali Danyelle M. Townsend Carolina de Aguiar Ferreira Ricardo Jose Alves Lucas Antonio Miranda Ferreira Andre Luis Branco de Barros |
| author_sort | Sued Eustaquio Mendes Miranda |
| collection | DOAJ |
| description | Breast cancer prevails as the most common cancer in women, underscoring an urgent need for more effective therapies. This study explores the potential of our newly developed nanoemulsion containing a novel fucoside derivative of lapachol (NE-F-LapA) as an intravenous treatment strategy. We sought to overcome the solubility issues associated with fucoside with this improved drug delivery strategy that enhances tumor delivery and mitigates other dose-limiting toxicities. Nanoemulsion was prepared and characterized by DLS, zeta potential, encapsulation efficiency, and storage stability. Cytotoxicity against breast cancer cell lines (4T1 and MDA-MB-231) and non-tumor human fibroblasts (NTHF) were evaluated. In vivo assays included antitumoral activity performance and acute systemic toxicity in mice models. NE-F-LapA was synthesized and optimized to 200 nm size, − 20 mV zeta potential, and near-complete (>98%) drug encapsulation. Stability exceeded 6 months, and biological fluid exposure maintained suitable properties for administration. In vitro, NE-F-LapA showed high toxicity (3 µM) against 4T1 and MDA-MB-231, enhanced five times the breast cancer cell uptake and three times the selectivity when compared to normal cells. Systemic toxicity assessment in mice revealed no concerning hematological or biochemical changes. Finally, in a 4T1 breast tumor model, NE-F-LapA significantly inhibited growth by 50% of the subcutaneous 4T1 tumor and reduced lung metastases 5-fold versus control. Overall, tailored nanoemulsification of the lapachol derivative enabled effective intravenous administration and improved efficacy over the free drug, indicating promise for enhanced breast cancer therapy pending further optimization. |
| first_indexed | 2024-03-08T16:33:10Z |
| format | Article |
| id | doaj.art-4fb50a2dc4654d829e31b29e7d94a4bc |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-08T16:33:10Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-4fb50a2dc4654d829e31b29e7d94a4bc2024-01-06T04:38:05ZengElsevierBiomedicine & Pharmacotherapy0753-33222024-01-01170116054Preclinical evaluation of L-fucoside from lapachol-loaded nanoemulsion as a strategy to breast cancer treatmentSued Eustaquio Mendes Miranda0Janaina de Alcantara Lemos1Flaviano Melo Ottoni2Geovanni Dantas Cassali3Danyelle M. Townsend4Carolina de Aguiar Ferreira5Ricardo Jose Alves6Lucas Antonio Miranda Ferreira7Andre Luis Branco de Barros8Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil; Department of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, BrazilDepartment of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, BrazilDepartment of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, BrazilDepartment of General Pathology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, BrazilDepartment of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC, USADepartments of Radiology, Pharmacology & Toxicology and Biomedical Engineering, Michigan State University, East Lansing, MI, USA; Corresponding authors.Department of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, BrazilDepartment of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, BrazilDepartment of Clinical and Toxicological Analysis, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil; Corresponding authors.Breast cancer prevails as the most common cancer in women, underscoring an urgent need for more effective therapies. This study explores the potential of our newly developed nanoemulsion containing a novel fucoside derivative of lapachol (NE-F-LapA) as an intravenous treatment strategy. We sought to overcome the solubility issues associated with fucoside with this improved drug delivery strategy that enhances tumor delivery and mitigates other dose-limiting toxicities. Nanoemulsion was prepared and characterized by DLS, zeta potential, encapsulation efficiency, and storage stability. Cytotoxicity against breast cancer cell lines (4T1 and MDA-MB-231) and non-tumor human fibroblasts (NTHF) were evaluated. In vivo assays included antitumoral activity performance and acute systemic toxicity in mice models. NE-F-LapA was synthesized and optimized to 200 nm size, − 20 mV zeta potential, and near-complete (>98%) drug encapsulation. Stability exceeded 6 months, and biological fluid exposure maintained suitable properties for administration. In vitro, NE-F-LapA showed high toxicity (3 µM) against 4T1 and MDA-MB-231, enhanced five times the breast cancer cell uptake and three times the selectivity when compared to normal cells. Systemic toxicity assessment in mice revealed no concerning hematological or biochemical changes. Finally, in a 4T1 breast tumor model, NE-F-LapA significantly inhibited growth by 50% of the subcutaneous 4T1 tumor and reduced lung metastases 5-fold versus control. Overall, tailored nanoemulsification of the lapachol derivative enabled effective intravenous administration and improved efficacy over the free drug, indicating promise for enhanced breast cancer therapy pending further optimization.http://www.sciencedirect.com/science/article/pii/S0753332223018528LapacholTumorNanoemulsionDrug delivery |
| spellingShingle | Sued Eustaquio Mendes Miranda Janaina de Alcantara Lemos Flaviano Melo Ottoni Geovanni Dantas Cassali Danyelle M. Townsend Carolina de Aguiar Ferreira Ricardo Jose Alves Lucas Antonio Miranda Ferreira Andre Luis Branco de Barros Preclinical evaluation of L-fucoside from lapachol-loaded nanoemulsion as a strategy to breast cancer treatment Biomedicine & Pharmacotherapy Lapachol Tumor Nanoemulsion Drug delivery |
| title | Preclinical evaluation of L-fucoside from lapachol-loaded nanoemulsion as a strategy to breast cancer treatment |
| title_full | Preclinical evaluation of L-fucoside from lapachol-loaded nanoemulsion as a strategy to breast cancer treatment |
| title_fullStr | Preclinical evaluation of L-fucoside from lapachol-loaded nanoemulsion as a strategy to breast cancer treatment |
| title_full_unstemmed | Preclinical evaluation of L-fucoside from lapachol-loaded nanoemulsion as a strategy to breast cancer treatment |
| title_short | Preclinical evaluation of L-fucoside from lapachol-loaded nanoemulsion as a strategy to breast cancer treatment |
| title_sort | preclinical evaluation of l fucoside from lapachol loaded nanoemulsion as a strategy to breast cancer treatment |
| topic | Lapachol Tumor Nanoemulsion Drug delivery |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223018528 |
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