Development of chitosan-pullulan composite nanoparticles for nasal delivery of vaccines: optimisation and cellular studies.
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.
a Department of Pharmaceutical Technology, Faculty of Pharmacy , Istanbul University , Istanbul , Turkey .
Erdal
E
Cevher
b Department of Pharmaceutics , The UCL School of Pharmacy, University of London , London , UK .|c GlaxoSmithKline , London , UK .
Stefan K
SK
Salomon
b Department of Pharmaceutics , The UCL School of Pharmacy, University of London , London , UK .
Apostolos
A
Makrakis
b Department of Pharmaceutics , The UCL School of Pharmacy, University of London , London , UK .|d PsiOxus Therapeutics Ltd. , Abingdon , Oxfordshire , UK , and.
Xiong Wei
XW
Li
b Department of Pharmaceutics , The UCL School of Pharmacy, University of London , London , UK .
Steve
S
Brocchini
b Department of Pharmaceutics , The UCL School of Pharmacy, University of London , London , UK .|e Department of Pharmaceutics, Faculty of Pharmacy , Kemerburgaz University , Istanbul , Turkey.
H Oya
HO
Alpar
D000281:Administration, Intranasal; D000818:Animals; D002460:Cell Line; D048271:Chitosan / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D005936:Glucans / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D051379:Mice; D053761:Nanocomposites / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D014612:Vaccines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
D005936:Glucans; D014612:Vaccines; C410955:carboxymethylpullulan; D048271:Chitosan
Carboxymethyl pullulan; N-trimethyl chitosan chloride; cellular uptake; chitosan derivatives; nanoparticles; nasal vaccination; polyion complexation