Development of chitosan–pullulan composite nanoparticles for nasal delivery of vaccines: optimisation and cellular studies

Abstract

Nasal immunisation with nanoparticles has already shown promising results. In this study, nanoparticle composites carrying BSA for nasal vaccination prepared using electrostatic interaction process between polycation N-trimethyl chitosan chloride (TMC), chitosan glutamate (CG), chitosan chloride (CCl) and polyanion carboxymethyl pullulan (CMP). A mass ratio of 2:1 for TMC-CMP combination produced stable nanocarriers. For CCl-CMP and CG-CMP formulations needed a mass ratio of 3:1. Loading efficiency was >90% for all formulations. Nanoparticles' size ranged from 207 to 603 nm. The surface charge of the complexes varied between +14 and +33 mV. SDS-PAGE integrity of the model antigen was also demonstrated. MTT studies showed that nanoparticle composites were less toxic to Calu-3 cells than the particles of cationic polymers alone. FITC-BSA loaded nanoparticles efficiently taken up by J774A.1 macrophages as confirmed by confocal microscopy highlighting the potential of these novel nanoparticulate carriers' use for nasal vaccination.

Overviews on the cellular uptake mechanism of polysaccharide colloidal nanoparticles

“…Much stronger complexation between N ‐trimethyl CS chloride and CMP resulted in smaller particle size when compared with CS salts. In mouse macrophages (J774A.1), the highest uptake efficiency was found with N ‐trimethyl CS chloride–CMP composite particles after 2‐hrs incubation which could be explained by their smaller dimension and more narrow particle size distribution .…”

“…Carboxymethyl pullulan (CMP) was reported as a polyanion for the first time to prepare composite nanoparticles for delivery of vaccines . The process of carboxymethylation enhances solubility of pullulan in cold water, and adding carboxylate groups along the polymer backbone provides a negative charge which is then allowed to react with polycations to form stable nanocomplexes during polyion complexation .…”

“…It has been found that CHP nanoparticles are effectively transferred to antigen‐presenting cells such as DCs and/or macrophages, allowing for a stronger immune response . Besides, CHP nanoparticles have been widely exploited in the nasal vaccine delivery because of their ability to adhere to the nasal epithelium . Figure shows the uptake of vaccine antigen‐loaded CHP nanoparticles by nasal dendritic cells as a result of the induction of antigen specific responses.…”

The efficacy of sustained-release chitosan microspheres containing recombinant human parathyroid hormone on MRONJ

“…separation of particles, reducing the extent of aggregation caused by Van de Waals interactions. 29 In this study, microsphere formulations resulted in positive zeta potential value of between +16.5 mV and +18.7 mV; the polymer:TPP mass ratio did not significantly influence the surface charge of the microspheres. Particle morphology was evaluated by SEM.…”

Polysaccharide Based Nanoparticles

“…Prepared nanoparticles showed good drug release. Cevher and coworkers synthesized nanoparticles by electrostatic interaction between negatively charged CMP and positively charged CS derivatives (N‐trimethyl CS chloride, CS glutamate, CS chloride) and reported that a significantly low cytotoxic activity in respiratory cells (Calu‐3 cells) than that of the CS derivatives, alone. Also highest uptake efficiency was found with N‐trimethyl CS chloride−CMP composite particles after 2‐hrs incubation which was due to their smaller size and narrow particle size distribution.…”