Curcumin/poly(2-methyl-2-oxazoline-b-tetrahydrofuran-b-2-methyl-2-oxazoline) formulation: An improved penetration and biological effect of curcumin in F508del-CFTR cell lines

• Published in: European journal of pharmaceutics and biopharmaceutics 2017-08, Vol.117, p.168-181
• Main Authors: Gonçalves, Cristine, Gomez, Jean-Pierre, Même, William, Rasolonjatovo, Bazoly, Gosset, David, Nedellec, Steven, Hulin, Philippe, Huin, Cécile, Le Gall, Tony, Montier, Tristan, Lehn, Pierre, Pichon, Chantal, Guégan, Philippe, Cheradame, Hervé, Midoux, Patrick
• Format: Article
• Language: English
• Subjects: Amphiphilic polymer; Animals; Cell Line; Cell Membrane Permeability - drug effects; Cell Membrane Permeability - physiology; CFTR; Curcumin; Curcumin - chemistry; Curcumin - metabolism; Curcumin - pharmacology; Cystic fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator - metabolism; Dose-Response Relationship, Drug; Drug Compounding; Furans - chemistry; Furans - metabolism; Furans - pharmacology; Galenic pharmacology; Humans; Life Sciences; Mice; Oxazoles - chemistry; Oxazoles - metabolism; Oxazoles - pharmacology; Pharmaceutical sciences; Pharmacology; Respiratory Mucosa - drug effects; Respiratory Mucosa - metabolism; Triblock copolymer
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2017.04.015

[Display omitted] Neutral amphiphilic triblock ABA copolymers are of great interest to solubilize hydrophobic drugs. We reported that a triblock ABA copolymer consisting of methyl-2-oxazoline (MeOx) and tetrahydrofuran (THF) (MeOx6-THF19-MeOx6) (TBCP2) can solubilize curcumin (Cur) a very hydrophobic molecule exhibiting multiple therapeutic effects but whose insolubility and low stability in water is a major drawback for clinical applications. Here, we provide evidences by flow cytometry and confocal microscopy that Cur penetration in normal and ΔF508-CFTR human airway epithelial cell lines is facilitated by TBCP2. When used on ΔF508-CFTR cell lines, the Cur/TBCP2 formulation promotes the restoration of the expression of the CFTR protein in the plasma membrane. Furthermore, patch-clamp and MQAE fluorescence experiments show that this effect is associated with a correction of a Cl− selective current at the membrane surface of F508del-CFTR cells. The results show the great potential of the neutral amphiphilic triblock copolymer MeOx6-THF19-MeOx6 as carrier for curcumin in a Cystic Fibrosis context. We anticipate that other MeOxn-THFm-MeOxn copolymers could have similar behaviours for other highly insoluble therapeutic drugs or cosmetic active ingredients.