TY - JOUR
T1 - Optimized acriflavine-loaded lipid nanocapsules as a safe and effective delivery system to treat breast cancer
AU - Montigaud, Yoann
AU - Ucakar, Bernard
AU - Krishnamachary, Balaji
AU - Bhujwalla, Zaver M.
AU - Feron, Olivier
AU - Préat, Véronique
AU - Danhier, Fabienne
AU - Gallez, Bernard
AU - Danhier, Pierre
N1 - Funding Information:
This study was supported by the Belgian National Fund for Scientific Research – Fonds National de la Recherche Scientifique (F.R.S.- FNRS) and the Fondation contre le cancer (Belgium). The authors have no conflicts of interest to declare.
Funding Information:
This study was supported by the Belgian National Fund for Scientific Research – Fonds National de la Recherche Scientifique (F.R.S.- FNRS) and the Fondation contre le cancer (Belgium). The authors have no conflicts of interest to declare.
Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2018/11/15
Y1 - 2018/11/15
N2 - 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.
AB - 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.
KW - 4T1 cells
KW - Acriflavine
KW - Breast cancer
KW - Design of experiments (DoE)
KW - Drug delivery system
KW - Lipid nanocapsules
UR - http://www.scopus.com/inward/record.url?scp=85053841103&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85053841103&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2018.09.034
DO - 10.1016/j.ijpharm.2018.09.034
M3 - Article
C2 - 30236645
AN - SCOPUS:85053841103
SN - 0378-5173
VL - 551
SP - 322
EP - 328
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 1-2
ER -