Mitoxantrone-loaded lipid nanoparticles for breast cancer therapy - Quality-by-design approach and efficacy assessment in 2D and 3D in vitro cancer models

• Tipo: Artigo em Revista Científica Internacional
• Data: 2021

Autores

Granja, A (Autor) Outra; Lima Sousa, R (Autor) Outra; Alves, CG (Autor) Outra; de Melo Diogo, D (Autor) Outra; Pinheiro, M (Autor) Outra; Sousa, CT (Autor) FCUP; Correia, IJ (Autor) Outra; Salette Reis (Autor) FFUP

Revista

Título: International Journal of Pharmaceutics

Vol. 607

ISSN: 0378-5173

Editora: Elsevier

Indexação

ISI Web of Knowledge - 9 Citações

Scopus - 12 Citações

Outras Informações

ID Authenticus: P-00V-BCF

DOI: 10.1016/j.ijpharm.2021.121044

Abstract (EN): Breast cancer is the leading cause of cancer-related deaths among women worldwide. The conventional chemotherapeutic regimens used in the treatment of this disease often lead to severe side-effects and reduced efficacy. In this study, a novel drug delivery system for the chemotherapeutic drug mitoxantrone (Mito) was developed using solid lipid nanoparticles (SLN). The production of the SLN was carried out using an organicsolvent-free, low-cost method and optimized using a Box-Behnken design. SLN presented adequate size for cancer-related applications, more than 90% of EE% and remained stable for at least 6 months. A much higher drug release was obtained at acidic pH (mimicking the endosomal compartment) than plasmatic pH, highlighting the potential of the nanosystem for tumor drug delivery. Additionally, SLN were non-hemolytic and cytocompatible, even at high concentrations of lipid. A significantly higher anti-cancer efficacy was obtained for Mitoloaded SLN comparing to the free drug at different concentrations in MCF-7 2D models. Finally, the nanoformulation was evaluated in heterotypic breast cancer spheroids showing capacity to penetrate the tridimensional structure and ability to induce a high anti-tumoral effect, similarly to the free drug. Overall, these results support that the developed SLN are effective Mito nanocarriers for the treatment of breast cancer.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 11