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Hepatitis B surface antigen nanoparticles coated with chitosan and trimethyl chitosan: Impact of formulation on physicochemical and immunological characteristics.
Vaccine. 2012 Aug 03; 30(36):5341-8.V

Abstract

Mucosal immunization offers various advantages over parenteral vaccination, but typically requires potent delivery systems and/or adjuvants to result in protective immunity. Here we report on the preparation of trimethylated chitosan (TMC) and chitosan (CHT) nanoparticles (NPs) loaded with hepatitis B surface antigen (HB), by a simple and scalable method. TMC:HB and CHT:HB NPs were prepared by direct coating of antigen by polymer. The impact of buffer, pH and tonicity of the dispersion medium on NPs' polydispersity, zeta potential and association percentage of polymer with antigen was evaluated. Moreover, biological properties of both NPs were addressed in vitro by studying their effect on cell viability, transepithelial electrical resistance (TEER) and dendritic cell (DC) maturation. Finally, immunogenicity was assessed by evaluating IgG, IgG1, IgG2a, IgA titers and sIgA after both mucosal (nasal) as well intramuscular (i.m.) vaccination in a murine model. TMC:HB and CHT:HB NPs, prepared in acetate buffer pH 6.7 of three different tonicities, had comparable size, polydispersity, zeta potential and association percentage. TMC:HB NPs, but not CHT:HB NPs, had a mild negative effect on cell viability and TEER, and a considerable positive effect on DC maturation. After nasal and i.m. immunization, TMC:HB NPs in hypotonic medium and CHT:HB NPs in all media induced higher serum and nasal antibody titers compared with HB solution (P<0.001). After i.m. injection, both TMC:HB and CHT:HB NPs induced higher IgG and IgG2a titers compared with alum adsorbed HB (P<0.001). For CHT:HB NPs, the tonicity of the dispersion medium did not affect the mucosal and systemic immune responses. In conclusion, TMC NPs and CHT NPs are similarly potent mucosal immunoadjuvants for HB. Moreover, both polymers are potent immunoadjuvants for i.m. administered isotonic HB, resulting in higher IgG2a/IgG1 ratios compared with alum adjuvanted HB.

Authors+Show Affiliations

Division of Drug Delivery Technology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22749834

Citation

Tafaghodi, Mohsen, et al. "Hepatitis B Surface Antigen Nanoparticles Coated With Chitosan and Trimethyl Chitosan: Impact of Formulation On Physicochemical and Immunological Characteristics." Vaccine, vol. 30, no. 36, 2012, pp. 5341-8.
Tafaghodi M, Saluja V, Kersten GF, et al. Hepatitis B surface antigen nanoparticles coated with chitosan and trimethyl chitosan: Impact of formulation on physicochemical and immunological characteristics. Vaccine. 2012;30(36):5341-8.
Tafaghodi, M., Saluja, V., Kersten, G. F., Kraan, H., Slütter, B., Amorij, J. P., & Jiskoot, W. (2012). Hepatitis B surface antigen nanoparticles coated with chitosan and trimethyl chitosan: Impact of formulation on physicochemical and immunological characteristics. Vaccine, 30(36), 5341-8. https://doi.org/10.1016/j.vaccine.2012.06.035
Tafaghodi M, et al. Hepatitis B Surface Antigen Nanoparticles Coated With Chitosan and Trimethyl Chitosan: Impact of Formulation On Physicochemical and Immunological Characteristics. Vaccine. 2012 Aug 3;30(36):5341-8. PubMed PMID: 22749834.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hepatitis B surface antigen nanoparticles coated with chitosan and trimethyl chitosan: Impact of formulation on physicochemical and immunological characteristics. AU - Tafaghodi,Mohsen, AU - Saluja,Vinay, AU - Kersten,Gideon F A, AU - Kraan,Heleen, AU - Slütter,Bram, AU - Amorij,Jean-Pierre, AU - Jiskoot,Wim, Y1 - 2012/06/27/ PY - 2012/01/22/received PY - 2012/06/09/revised PY - 2012/06/13/accepted PY - 2012/7/4/entrez PY - 2012/7/4/pubmed PY - 2012/12/22/medline SP - 5341 EP - 8 JF - Vaccine JO - Vaccine VL - 30 IS - 36 N2 - Mucosal immunization offers various advantages over parenteral vaccination, but typically requires potent delivery systems and/or adjuvants to result in protective immunity. Here we report on the preparation of trimethylated chitosan (TMC) and chitosan (CHT) nanoparticles (NPs) loaded with hepatitis B surface antigen (HB), by a simple and scalable method. TMC:HB and CHT:HB NPs were prepared by direct coating of antigen by polymer. The impact of buffer, pH and tonicity of the dispersion medium on NPs' polydispersity, zeta potential and association percentage of polymer with antigen was evaluated. Moreover, biological properties of both NPs were addressed in vitro by studying their effect on cell viability, transepithelial electrical resistance (TEER) and dendritic cell (DC) maturation. Finally, immunogenicity was assessed by evaluating IgG, IgG1, IgG2a, IgA titers and sIgA after both mucosal (nasal) as well intramuscular (i.m.) vaccination in a murine model. TMC:HB and CHT:HB NPs, prepared in acetate buffer pH 6.7 of three different tonicities, had comparable size, polydispersity, zeta potential and association percentage. TMC:HB NPs, but not CHT:HB NPs, had a mild negative effect on cell viability and TEER, and a considerable positive effect on DC maturation. After nasal and i.m. immunization, TMC:HB NPs in hypotonic medium and CHT:HB NPs in all media induced higher serum and nasal antibody titers compared with HB solution (P<0.001). After i.m. injection, both TMC:HB and CHT:HB NPs induced higher IgG and IgG2a titers compared with alum adsorbed HB (P<0.001). For CHT:HB NPs, the tonicity of the dispersion medium did not affect the mucosal and systemic immune responses. In conclusion, TMC NPs and CHT NPs are similarly potent mucosal immunoadjuvants for HB. Moreover, both polymers are potent immunoadjuvants for i.m. administered isotonic HB, resulting in higher IgG2a/IgG1 ratios compared with alum adjuvanted HB. SN - 1873-2518 UR - https://www.unboundmedicine.com/medline/citation/22749834/Hepatitis_B_surface_antigen_nanoparticles_coated_with_chitosan_and_trimethyl_chitosan:_Impact_of_formulation_on_physicochemical_and_immunological_characteristics_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0264-410X(12)00890-0 DB - PRIME DP - Unbound Medicine ER -