Gelation and micellization behaviors of pluronic(®) F127 hydrogel containing poly(isobutylcyanoacrylate) nanoparticles specifically designed for mucosal application.
The aim of this investigation is to combine the advantages of pluronic(®) F127 hydrogels and nanoparticles composed of poly(isobutylcyanoacrylate) (PIBCA) core coated with a mixture of chitosan and thiolated chitosan to design novel multifunctional formulation for mucosal application. Nanoparticles offer the advantage of being mucoadhesive while pluronic(®) F127 hydrogel allowed prolonged contact time onto mucosal surfaces. This work highlights an unprecedented comprehensive study on the effect of nanoparticles on gelation and micellization behaviors of pluronic(®) F127 using rheology and micro-calorimetry experiments. Results showed that presence of nanoparticles induced (i) smaller crystal peak of F127, (ii) a decrease of the enthalpy of F127 micellization and (iii) a non-reversibility of micelle formation (during heating ramp) and micelle melting (during cooling ramp). Together, these findings suggest that a part of F127 was not able to associate into micelles and the formation of mixed micelles containing F127 unimers and PIBCA/(chitosan/thiolated chitosan) copolymer and/or PIBCA homopolymer was suspected. The interaction of F127 unimers with nanoparticles resulted from their physical de-structuration as revealed by nanoparticle size measurement. In addition, we found that short polymerization duration of one hour induced more pronounced nanoparticle de-structuration. Twenty-four hour-polymerization of isobutylcyanoacrylate in the presence of chitosan and thiolated chitosan led to more stable nanoparticles when mixed with pluronic(®) F127.
Institut Galien Paris Sud, UMR CNRS 8612, Université Paris-Sud, Faculté de Pharmacie, 5, rue J-B. Clément, 92296, Châtenay-Malabry Cedex, France; BioCis, Biomolécules : conception, isolement, synthèse- Chimiothérapie Antiparasitaire, UMR CNRS 8076, Université Paris-Sud, Faculté de Pharmacie, 5, rue J.B. Clément, 92296 Châtenay-Malabry Cedex, France; Laboratoire de Physique Thermique, ESPCI-ParisTech, PSL Research University, 10 rue Vauquelin, 75231 Paris Cedex 05, France.
Bénédicte
B
Pradines
Laboratoire de Physique Thermique, ESPCI-ParisTech, PSL Research University, 10 rue Vauquelin, 75231 Paris Cedex 05, France.
Madeleine
M
Djabourov
Institut Galien Paris Sud, UMR CNRS 8612, Université Paris-Sud, Faculté de Pharmacie, 5, rue J-B. Clément, 92296, Châtenay-Malabry Cedex, France.
Christine
C
Vauthier
BioCis, Biomolécules : conception, isolement, synthèse- Chimiothérapie Antiparasitaire, UMR CNRS 8076, Université Paris-Sud, Faculté de Pharmacie, 5, rue J.B. Clément, 92296 Châtenay-Malabry Cedex, France.
Philippe M
PM
Loiseau
Institut Galien Paris Sud, UMR CNRS 8612, Université Paris-Sud, Faculté de Pharmacie, 5, rue J-B. Clément, 92296, Châtenay-Malabry Cedex, France.
Gilles
G
Ponchel
Institut Galien Paris Sud, UMR CNRS 8612, Member of the Institut Universitaire de France (IUF), Université Paris-Sud, Faculté de Pharmacie, 5, rue J-B. Clément, 92296, Châtenay-Malabry Cedex, France. Electronic address: kawthar.bouchemal@u-psud.fr.
Kawthar
K
Bouchemal
D002152:Calorimetry, Differential Scanning; D003487:Cyanoacrylates / Q000737:chemistry*; D004659:Enbucrilate; D020100:Hydrogels; D008823:Micelles; D009092:Mucous Membrane; D053758:Nanoparticles; D020442:Poloxamer / Q000737:chemistry*; D058105:Polymerization; D012212:Rheology
D003487:Cyanoacrylates; D020100:Hydrogels; D008823:Micelles; D020442:Poloxamer; D004659:Enbucrilate
Chitosan; Hydrogel; Isobutylcyanoacrylate; Mucoadhesive; Nanoparticles; Thermosensitive