Chitosan coated human serum albumin nanoparticles: A promising strategy for nose-to-brain drug delivery

The aim of the present study was the development of human serum albumin nanoparticles (HSA NPs) as nose-to-brain carrier. To strengthen, the efficacy of nanoparticles as drug delivery system, the influence of chitosan (CS) coating on the performance of HSA NPs was investigated for nasal application. HSA NPs were prepared by desolvation technique. CS coating was obtained adding the CS solution to HSA NPs. The mean particle sizes was 241 ± 18 nm and 261 ± 8 nm and the ζ-potential was −47 ± 3 mV and + 45 ± 1 mV for HSA NPs and CS-HSA NPs, respectively. The optimized formulations showed excellent stability upon storage both as suspension and as freeze-dried product after 3 months. The mucoadhesion properties were assessed by turbidimetric and indirect method. NPs were loaded with sulforhodamine B sodium salt as model drug and the effect of CS coating was investigated performing release studies, permeation and uptake experiments using Caco-2 and hCMEC/D3 cells as model of the nasal epithelium and blood-brain barrier, respectively. Furthermore, ex vivo diffusion experiments have been carried out using rabbit nasal mucosa. Finally, the ability of the formulations to reversibly open tight and gap junctions was explored by western blotting and RT-PCR analyzing in both Caco-2 and hCMEC/D3 cells.