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

• Type: Article in International Scientific Journal
• Date: 2021

Authors

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

Journal

Title: International Journal of Pharmaceutics

Vol. 607

ISSN: 0378-5173

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 9 Citations

Scopus - 12 Citations

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11