Mucoadhesive acrylated block copolymers micelles for the delivery of hydrophobic drugs

Blockpolymer micelles having acrylated end groups were fabricated for the development of mucoadhesive drug loaded vehicle. The critical micelle concentration (CMC) of Pluronic (R) F127 modified with acrylate end groups (F127DA) was found to be similar to that of the unmodified Pluronic (R) F127 (F127). Small angle X-ray scattering verified existence of micelles with an inner core of 4.9 +/- 0.2 and 5.5 +/- 0.3 for F127 and F127DA respectively. Indomethacin, a hydrophobic drug, was incorporated into the micelles using the thin-film hydration method. In vitro drug release assay demonstrated that the micelles sustained the release of the drug in comparison with free drug in solution. Several methods were used for mucoadhesion evaluation. Viscosity profiling was performed by shear rate sweep experiment of hydrated commercial mucin, F127 or F127DA, and combination of both mucin and a copolymer. Elevated viscosity was achieved for acrylated micelles with mucin compared to mixtures of non-acrylated micelles with mucin. The mucoadhesivity of the acrylated micelles was further characterized using nuclear magnetic resonance (NMR); data affirmed the Michael type addition reaction occurred between acrylates on the micelles corona and thiols present in the mucin. SAXS scattering data further showed a modification in the scattering of F127DA micelles with the addition of pig gastric mucin. Cryo-transmission electron microscopy (cryo-TEM) and dynamic light scattering (DLS) data detected increase in the aggregates size while using acrylated micelles enhance mucoadhesion. Thus acrylated F127DA micelles were found to be mucoadhesive, and a suitable and preferred candidate for micellar drug delivery to mucosal surfaces. (C) 2015 Elsevier B.V. All rights reserved.