TY - JOUR

T1 - Comparison of chitosan nanoparticles and chitosan hydrogels for vaccine delivery

AU - Gordon, Sarah

AU - Saupe, Anne

AU - McBurney, Warren

AU - Rades, Thomas

AU - Hook, Sarah

PY - 2008

Y1 - 2008

N2 - In this work the potential of chitosan nanoparticles (CNP) and thermosensitive chitosan hydrogels as particulate and sustained release vaccine delivery systems was investigated. CNP and chitosan hydrogels were prepared, loaded with the model protein antigen ovalbumin (OVA) and characterised. The immunostimulatory capacity of these vaccine delivery systems was assessed in-vitro and in-vivo. Particle sizing measurements and SEM images showed that optimised OVA-loaded CNP had a size of approximately 200 nm, a polydispersity index <0.2, and a positive zeta-potential of approximately 18 mV. The amount of OVA adsorbed onto CNP was high with an adsorption efficacy of greater than 96%. Raman spectroscopy indicated conformational changes of OVA when adsorbed onto the surface of CNP. Uptake of the dispersions and immunological activation of murine dendritic cells in-vitro could be demonstrated. Investigation of the release of fluorescently-labelled OVA (FITC-OVA) from CNP and chitosan hydrogels in-vitro showed that approximately 50% of the total protein was released from CNP within a period of ten days; release of antigen from chitosan gel occurred in a more sustained manner, with <10% of total protein being released after 10 days. The slow release from gel formulations may be explained by the strong interactions of the protein with chitosan. While OVA-loaded CNP showed no significant immunogenicity, formulations of OVA in chitosan gel were able to stimulate both cell-mediated and humoral immunity in-vivo.

AB - In this work the potential of chitosan nanoparticles (CNP) and thermosensitive chitosan hydrogels as particulate and sustained release vaccine delivery systems was investigated. CNP and chitosan hydrogels were prepared, loaded with the model protein antigen ovalbumin (OVA) and characterised. The immunostimulatory capacity of these vaccine delivery systems was assessed in-vitro and in-vivo. Particle sizing measurements and SEM images showed that optimised OVA-loaded CNP had a size of approximately 200 nm, a polydispersity index <0.2, and a positive zeta-potential of approximately 18 mV. The amount of OVA adsorbed onto CNP was high with an adsorption efficacy of greater than 96%. Raman spectroscopy indicated conformational changes of OVA when adsorbed onto the surface of CNP. Uptake of the dispersions and immunological activation of murine dendritic cells in-vitro could be demonstrated. Investigation of the release of fluorescently-labelled OVA (FITC-OVA) from CNP and chitosan hydrogels in-vitro showed that approximately 50% of the total protein was released from CNP within a period of ten days; release of antigen from chitosan gel occurred in a more sustained manner, with <10% of total protein being released after 10 days. The slow release from gel formulations may be explained by the strong interactions of the protein with chitosan. While OVA-loaded CNP showed no significant immunogenicity, formulations of OVA in chitosan gel were able to stimulate both cell-mediated and humoral immunity in-vivo.

KW - Animals

KW - Chemistry, Pharmaceutical

KW - Chitosan

KW - Delayed-Action Preparations

KW - Drug Carriers

KW - Hot Temperature

KW - Hydrogels

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Transgenic

KW - Microscopy, Electron, Scanning

KW - Nanoparticles

KW - Ovalbumin

KW - Particle Size

KW - Spectrum Analysis, Raman

KW - Vaccines

U2 - 10.1211/jpp/60.12.0004

DO - 10.1211/jpp/60.12.0004

M3 - Journal article

C2 - 19000363

VL - 60

SP - 1591

EP - 1600

JO - Journal of Pharmacy and Pharmacology

JF - Journal of Pharmacy and Pharmacology

SN - 0022-3573

IS - 12

ER -