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Preclinical evaluation of L-fucoside from lapachol-loaded nanoemulsion as a strategy to breast cancer treatment.
Miranda, Sued Eustaquio Mendes; de Alcantara Lemos, Janaina; Ottoni, Flaviano Melo; Cassali, Geovanni Dantas; Townsend, Danyelle M; de Aguiar Ferreira, Carolina; Alves, Ricardo Jose; Ferreira, Lucas Antonio Miranda; de Barros, Andre Luis Branco.
Afiliación
  • Miranda SEM; Department 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, Brazil.
  • de Alcantara Lemos J; Department of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil.
  • Ottoni FM; Department of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil.
  • Cassali GD; Department of General Pathology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
  • Townsend DM; Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC, USA.
  • de Aguiar Ferreira C; Departments of Radiology, Pharmacology & Toxicology and Biomedical Engineering, Michigan State University, East Lansing, MI, USA. Electronic address: deaguia1@msu.edu.
  • Alves RJ; Department of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil.
  • Ferreira LAM; Department of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil.
  • de Barros ALB; Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil. Electronic address: brancodebarros@yahoo.com.br.
Biomed Pharmacother ; 170: 116054, 2024 Jan.
Article en En | MEDLINE | ID: mdl-38150876
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Nanopartículas Límite: Animals / Female / Humans Idioma: En Revista: Biomed Pharmacother Año: 2024 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Francia

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Nanopartículas Límite: Animals / Female / Humans Idioma: En Revista: Biomed Pharmacother Año: 2024 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Francia