Design, optimization and in vitro evaluation of reverse micelle-loaded lipid nanocarriers containing erlotinib hydrochloride.
Erlotinib hydrochloride (ERLO) belongs to the tyrosine kinase inhibitor family and is used for the treatment of pancreatic cancers. In the present study, ERLO was entrapped in lipid nanocarriers by means of reverse micellar incorporation. This study aims to optimize the formulation of ERLO-loaded nanoparticles. Surfactants forming reverse micelles in Labrafac(®) were filled with ERLO under various conditions. Both the initial amount of drug incubated with reverse micelles and the surfactant composing the reverse micelles are crucial parameters for reverse micelle capacity to load ERLO. The optimal loading system for reverse micelles was obtained with a mix of sorbitan trioleate (Span(®) 85) and Labrafac(®) oil at a 1:1 (w/w) ratio. Reverse micelle composition influenced the nanocarrier's hydrodynamic diameter, polydispersity index, and zeta potential. In lipid nanoparticles formulated by using the phase inversion temperature (PIT) method, ERLO entrapment efficiency was around 56%. In vitro, the efficacy of ERLO-loaded nanocarriers on BxPC-3 pancreatic adenocarcinoma cells was comparable to free ERLO, and led to a cell death rate of around 40%.
LUNAM Université, Université d'Angers, INSERM U1066-MINT - Micro et Nanomédecines Biomimétiques, IBS-CHU Angers, 4 rue Larrey, F-49933 Angers, France. sandy-vrignaud@hotmail.fr
Sandy
S
Vrignaud
José
J
Hureaux
Séverine
S
Wack
Jean-Pierre
JP
Benoit
Patrick
P
Saulnier
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D000069347:Erlotinib Hydrochloride; D006801:Humans; D008823:Micelles; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000737:chemistry*; D011799:Quinazolines / Q000008:administration & dosage / Q000737:chemistry*; D013501:Surface-Active Agents / Q000008:administration & dosage / Q000737:chemistry; D014280:Triglycerides / Q000008:administration & dosage / Q000737:chemistry*
D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D013501:Surface-Active Agents; D014280:Triglycerides; C542236:labrafac WL 1349; D000069347:Erlotinib Hydrochloride