Mucoadhesive nanogels by ionotropic crosslinking of chitosan-g-oligo(NiPAam) polymeric micelles as novel drug nanocarriers

Aim: To investigate a novel kind of mucoadhesive nanogel based on the supramolecular aggregation of chitosan-g-oligo(N-isopropylacrylamide) copolymers. Materials & methods: Copolymers were synthesized by the graft-free radical polymerization of N-isopropylacrylamide on chitosan. The aggregation was studied by dynamic light scattering and nanoparticle tracking analysis (NTA), the nanostructure by transmission electron microscopy(TEM)/cryo-TEM, the mucoadhesiveness in vitro with mucin and the cytocompatibility in Caco2 cells. Results: Copolymers (36-74% w/w N-isopropylacrylamide content) showed critical micellar concentration between 2.0 and 40.0 × 10^-3% w/v and micelles were nanometric and positively charged. Physical stabilization was achieved with ionotropic crosslinking. TEM/cryo-TEM revealed multimicellar aggregates with good mucoadhesion and cytocompatibility properties. Micellar systems (1-10% w/v) increased the solubility of efavirenz up to 1249-fold. Conclusion: Results support the potential of these nano-drug delivery systems for improved mucosal administration of hydrophobic drugs.