Optimized acriflavine-loaded lipid nanocapsules as a safe and effective delivery system to treat breast cancer

Yoann Montigaud; Bernard Ucakar; Balaji Krishnamachary; Zaver M Bhujwalla; Olivier Feron; Véronique Préat; Fabienne Danhier; Bernard Gallez; Pierre Danhier

doi:10.1016/j.ijpharm.2018.09.034

Optimized acriflavine-loaded lipid nanocapsules as a safe and effective delivery system to treat breast cancer

Int J Pharm. 2018 Nov 15;551(1-2):322-328. doi: 10.1016/j.ijpharm.2018.09.034. Epub 2018 Sep 17.

Authors

Yoann Montigaud¹, Bernard Ucakar², Balaji Krishnamachary³, Zaver M Bhujwalla⁴, Olivier Feron⁵, Véronique Préat², Fabienne Danhier², Bernard Gallez⁶, Pierre Danhier⁷

Affiliations

¹ Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Avenue Mounier 73, B1.73.12, 1200 Brussels, Belgium; Université catholique de Louvain, Louvain Drug Research Institute, Biomedical Magnetic Resonance Research Group Platform, Avenue Mounier 73, B1.73.08, 1200 Brussels, Belgium.
² Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Avenue Mounier 73, B1.73.12, 1200 Brussels, Belgium.
³ Division of Cancer Imaging Research, In Vivo Cellular and Molecular Imaging Center, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁴ Division of Cancer Imaging Research, In Vivo Cellular and Molecular Imaging Center, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵ Université catholique de Louvain, Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC), Avenue Mounier 53, B1.53.09, 1200 Brussels, Belgium.
⁶ Université catholique de Louvain, Louvain Drug Research Institute, Biomedical Magnetic Resonance Research Group Platform, Avenue Mounier 73, B1.73.08, 1200 Brussels, Belgium. Electronic address: bernard.gallez@uclouvain.be.
⁷ Université catholique de Louvain, Louvain Drug Research Institute, Nuclear and Electron Spin Technologies (NEST) Platform, Avenue Mounier 73, B1.73.07, 1200 Brussels, Belgium.

PMID: 30236645
DOI: 10.1016/j.ijpharm.2018.09.034

Abstract

Acriflavine (ACF) hydrochloride is currently repurposed as multimodal drug, inhibiting hypoxia-inducible factors (HIF) pathways and exerting cytotoxic properties. The aim of this study was to encapsulate ACF in reverse micelles and to incorporate this suspension in lipid nanocapsules (LNC). Designs of experiments were used to work under quality by design conditions. LNC were formulated using a phase-inversion temperature method, leading to an encapsulation efficiency around 80%. In vitro, the encapsulated drug presented similar cytotoxic activity and decrease in HIF activity in 4T1 cells compared to the free drug. In vivo, ACF-loaded nanoparticles (ACF dose of 5 mg/kg) demonstrated a higher antitumor efficacy compared to free ACF on an orthotopic model of murine breast cancer (4T1 cells). Moreover, the use of LNC allowed to drastically decrease the number of administrations compared to the free drug (2 versus 12 injections), suppressing the ACF-induced toxicity.

Keywords: 4T1 cells; Acriflavine; Breast cancer; Design of experiments (DoE); Drug delivery system; Lipid nanocapsules.

MeSH terms

Acriflavine / administration & dosage*
Animals
Cell Line, Tumor
Drug Carriers / administration & dosage*
Female
Hypoxia-Inducible Factor 1 / antagonists & inhibitors*
Lipids / administration & dosage*
Mammary Neoplasms, Experimental / drug therapy*
Mice
Mice, Inbred BALB C
Nanocapsules / administration & dosage*

Substances

Drug Carriers
Hypoxia-Inducible Factor 1
Lipids
Nanocapsules
Acriflavine