A Composite Nanosystem as a Potential Tool for the Local Treatment of Glioblastoma: Chitosan-Coated Solid Lipid Nanoparticles Embedded in Electrospun Nanofibers

Abstract

Glioblastoma multiforme (GBM) is one of the most prevalent and aggressive brain tumors for which there is currently no cure. A novel composite nanosystem (CN), consisting of chitosan-coated Solid Lipid Nanoparticles (c-SLN) embedded in O-carboxymethyl chitosan (O-CMCS)-containing nanofibers (NFs), was proposed as a potential tool for the local delivery of lipophilic anti-proliferative drugs. Coacervation was selected as a solvent-free method for the preparation of stearic acid (SA) and behenic acid (BA)-based SLN (SA-SLN and BA-SLN respectively). BA-SLN, containing 0.75% w/w BA sodium salt and 3% w/w poly(vinyl alcohol) (PVA), were selected for the prosecution of the work since they are characterized by the lowest size functional to their subsequent coating and incorporation in nanofibers. BA-SLN were coated with chitosan (CS) by means of a two-step coating method based on the physical absorption of positively charged CS chains on the SLN negative surface. Nile Red (NR), chosen as the hydrophobic model dye, was dissolved in a micellar solution of BA sodium salt and then added with a coacervating solution until pH ≅ 2.5 was reached. Immunocytochemistry analyses highlighted that CS-coated BA-SLN (c-BA-SLN) exhibited a higher accumulation in human glioblastoma cells (U-373) after 6 h than CS-free BA-SLN. Finally, the c-BA-SLN dispersion was blended with a solution consisting of freely soluble polymers (O-CMCS, poly(ethylene oxide) and poloxamer) and then electrospun to obtain NFs with a mean diameter equal to 850 nm. After the NFs dissolution in an aqueous media, c-BA-SLN maintained their physicochemical properties and zeta potential.