Gelation and micellization behaviors of pluronic® F127 hydrogel containing poly(isobutylcyanoacrylate) nanoparticles specifically designed for mucosal application

Abstract

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.