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Mono-N-carboxymethyl chitosan (MCC) and N-trimethyl chitosan (TMC) nanoparticles for non-invasive vaccine delivery.
Int J Pharm. 2008 Nov 03; 363(1-2):139-48.IJ

Abstract

Mucosal application of a vaccine can effectively induce both systemic and mucosal immune responses. In general, mucosal applications of antigens result in poor immune responses. Therefore, adjuvant/delivery systems are required to enhance the immune response. Chitosan is a cationic biopolymer which exerts advantages as a vaccine carrier due to its immune stimulating activity and bioadhesive properties that enhance cellular uptake and permeation as well as antigen protection. Similar effects are also shown by chitosan derivatives. In this study, the nanoparticulate systems were prepared by using differently charged chitosan derivatives, N-trimethyl chitosan (TMC, polycationic), and mono-N-carboxymethyl chitosan (MCC, polyampholytic) for mucosal immunisation. The derivatives were synthesised and characterised in-house. The aqueous dispersions of the derivatives were also prepared for comparison. The cytotoxicity studies (MTT assay) on Chinese hamster ovary (CHO-K1) cell lines showed that cell viability was in the order of MCC, chitosan and TMC. Nanoparticles were prepared using ionic gelation method and loaded with tetanus toxoid (TT). Nanoparticles with high loading efficacy (>90% m/m), particle size within the range of 40-400nm, with a negative surface charge for MCC and positive surface charge for TMC and chitosan were obtained. The structural integrity of the TT in the formulations was confirmed by SDS-PAGE electrophoresis analysis. The effective uptake of the FITC-BSA loaded nanoparticles into the cells was demonstrated by cellular uptake studies using J774A.1 cells. Immune responses induced by the formulations loaded with tetanus toxoid were studied in vivo in Balb/c mice. Enhanced immune responses were obtained with intranasal (i.n.) application of nanoparticle formulations. Chitosan and TMC nanoparticles which have positively charged surfaces induced higher serum IgG titres when compared to those prepared with MCC which are negatively charged and smaller in size. Nanoparticle formulations developed in this study can be used as promising adjuvant/delivery systems for mucosal immunisation.

Authors+Show Affiliations

Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Technology, Ankara, Turkey.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

18662762

Citation

Sayin, B, et al. "Mono-N-carboxymethyl Chitosan (MCC) and N-trimethyl Chitosan (TMC) Nanoparticles for Non-invasive Vaccine Delivery." International Journal of Pharmaceutics, vol. 363, no. 1-2, 2008, pp. 139-48.
Sayin B, Somavarapu S, Li XW, et al. Mono-N-carboxymethyl chitosan (MCC) and N-trimethyl chitosan (TMC) nanoparticles for non-invasive vaccine delivery. Int J Pharm. 2008;363(1-2):139-48.
Sayin, B., Somavarapu, S., Li, X. W., Thanou, M., Sesardic, D., Alpar, H. O., & Senel, S. (2008). Mono-N-carboxymethyl chitosan (MCC) and N-trimethyl chitosan (TMC) nanoparticles for non-invasive vaccine delivery. International Journal of Pharmaceutics, 363(1-2), 139-48. https://doi.org/10.1016/j.ijpharm.2008.06.029
Sayin B, et al. Mono-N-carboxymethyl Chitosan (MCC) and N-trimethyl Chitosan (TMC) Nanoparticles for Non-invasive Vaccine Delivery. Int J Pharm. 2008 Nov 3;363(1-2):139-48. PubMed PMID: 18662762.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mono-N-carboxymethyl chitosan (MCC) and N-trimethyl chitosan (TMC) nanoparticles for non-invasive vaccine delivery. AU - Sayin,B, AU - Somavarapu,S, AU - Li,X W, AU - Thanou,M, AU - Sesardic,D, AU - Alpar,H O, AU - Senel,S, Y1 - 2008/07/09/ PY - 2008/04/08/received PY - 2008/06/24/revised PY - 2008/06/28/accepted PY - 2008/7/30/pubmed PY - 2008/12/17/medline PY - 2008/7/30/entrez SP - 139 EP - 48 JF - International journal of pharmaceutics JO - Int J Pharm VL - 363 IS - 1-2 N2 - Mucosal application of a vaccine can effectively induce both systemic and mucosal immune responses. In general, mucosal applications of antigens result in poor immune responses. Therefore, adjuvant/delivery systems are required to enhance the immune response. Chitosan is a cationic biopolymer which exerts advantages as a vaccine carrier due to its immune stimulating activity and bioadhesive properties that enhance cellular uptake and permeation as well as antigen protection. Similar effects are also shown by chitosan derivatives. In this study, the nanoparticulate systems were prepared by using differently charged chitosan derivatives, N-trimethyl chitosan (TMC, polycationic), and mono-N-carboxymethyl chitosan (MCC, polyampholytic) for mucosal immunisation. The derivatives were synthesised and characterised in-house. The aqueous dispersions of the derivatives were also prepared for comparison. The cytotoxicity studies (MTT assay) on Chinese hamster ovary (CHO-K1) cell lines showed that cell viability was in the order of MCC, chitosan and TMC. Nanoparticles were prepared using ionic gelation method and loaded with tetanus toxoid (TT). Nanoparticles with high loading efficacy (>90% m/m), particle size within the range of 40-400nm, with a negative surface charge for MCC and positive surface charge for TMC and chitosan were obtained. The structural integrity of the TT in the formulations was confirmed by SDS-PAGE electrophoresis analysis. The effective uptake of the FITC-BSA loaded nanoparticles into the cells was demonstrated by cellular uptake studies using J774A.1 cells. Immune responses induced by the formulations loaded with tetanus toxoid were studied in vivo in Balb/c mice. Enhanced immune responses were obtained with intranasal (i.n.) application of nanoparticle formulations. Chitosan and TMC nanoparticles which have positively charged surfaces induced higher serum IgG titres when compared to those prepared with MCC which are negatively charged and smaller in size. Nanoparticle formulations developed in this study can be used as promising adjuvant/delivery systems for mucosal immunisation. SN - 0378-5173 UR - https://www.unboundmedicine.com/medline/citation/18662762/Mono_N_carboxymethyl_chitosan__MCC__and_N_trimethyl_chitosan__TMC__nanoparticles_for_non_invasive_vaccine_delivery_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(08)00463-8 DB - PRIME DP - Unbound Medicine ER -