Effective transcutaneous immunization by antigen-loaded flexible liposome in vivo

Ni Li1, Li-Hua Peng1, Xi Chen1, Shinsaku Nakagawa2, Jian-Qing Gao11Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, People&#39;s Republic of China; 2Department of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Science...

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Autores principales:	Li N, Peng LH, Chen X, Nakagawa S, Gao JQ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2011
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/2bd338036757493d9fbc2131652e63dd
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spelling	oai:doaj.org-article:2bd338036757493d9fbc2131652e63dd2021-12-02T07:20:23ZEffective transcutaneous immunization by antigen-loaded flexible liposome in vivo1176-91141178-2013https://doaj.org/article/2bd338036757493d9fbc2131652e63dd2011-12-01T00:00:00Zhttp://www.dovepress.com/effective-transcutaneous-immunization-by-antigen-loaded-flexible-lipos-a8820https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Ni Li1, Li-Hua Peng1, Xi Chen1, Shinsaku Nakagawa2, Jian-Qing Gao11Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, People&#39;s Republic of China; 2Department of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, JapanBackground: Transcutaneous vaccines have received wide attention due to their easy-to-use, needle-free, noninvasive delivery. However, the novel barrier function of stratum corneum hinders the transport of antigen and adjuvant in transcutaneous immunization. Novel nanoscale delivery systems employing, for example, liposomes and nanoparticles, have been widely investigated to overcome the penetration barrier of stratum corneum for effective transcutaneous immunization.Objective: The objective of this study was to prepare two types of flexible liposomes and determine their efficacies for the transcutaneous delivery of antigen and the subsequent immune response induced in vivo.Methods: Ovalbumin (OVA) liposome-based transcutaneous vaccines were prepared using reverse-phase evaporation and film-dispersion methods. Particle sizes and antigen encapsulating efficiency were then evaluated. After application to bare mouse skin, topical sites were examined for the presence of fluorescence-labeled liposome. The efficacy of the transcutaneously delivered OVA-loaded flexible liposome in activating the immune responses was investigated by detecting serum immunoglobulin G levels. The influence of an adjuvant, imiquimod, in the transcutaneous immunization was also tested.Results: Two flexible liposomes with well-encapsulated OVA were successfully prepared by film-dispersion or reverse-phase evaporation methods. The sizes of the prepared flexible liposomes ranged from 200 to 400 nm. In vivo, the fluorescence-labeled liposome was detected in hair-follicle ducts, indicating that the flexible liposome can penetrate the skin barrier through the hair follicles. Upon transcutaneous administration, the OVA-encapsulated flexible liposome elicited a strong immune response similar to that of positive control (ie, OVA solution administrated by subcutaneous injection with Al(OH)3 as an adjuvant). Co-administration of imiquimod with the OVA-loaded liposome expressed a significant enhancement on the transcutaneous immune responses.Conclusion: Results of this study highlight the nanoscale formulation, flexible liposome, as a promising carrier for the transcutaneous delivery of antigen proteins. Imiquimod was shown to be an effective adjuvant as a transcutaneous immunization enhancer with the potential for transcutaneous vaccine development.Keywords: flexible liposome, transcutaneous vaccine, immunization enhancement, adjuvantLi NPeng LHChen XNakagawa SGao JQDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2011, Iss default, Pp 3241-3250 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Li N Peng LH Chen X Nakagawa S Gao JQ Effective transcutaneous immunization by antigen-loaded flexible liposome in vivo
description	Ni Li1, Li-Hua Peng1, Xi Chen1, Shinsaku Nakagawa2, Jian-Qing Gao11Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, People&#39;s Republic of China; 2Department of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, JapanBackground: Transcutaneous vaccines have received wide attention due to their easy-to-use, needle-free, noninvasive delivery. However, the novel barrier function of stratum corneum hinders the transport of antigen and adjuvant in transcutaneous immunization. Novel nanoscale delivery systems employing, for example, liposomes and nanoparticles, have been widely investigated to overcome the penetration barrier of stratum corneum for effective transcutaneous immunization.Objective: The objective of this study was to prepare two types of flexible liposomes and determine their efficacies for the transcutaneous delivery of antigen and the subsequent immune response induced in vivo.Methods: Ovalbumin (OVA) liposome-based transcutaneous vaccines were prepared using reverse-phase evaporation and film-dispersion methods. Particle sizes and antigen encapsulating efficiency were then evaluated. After application to bare mouse skin, topical sites were examined for the presence of fluorescence-labeled liposome. The efficacy of the transcutaneously delivered OVA-loaded flexible liposome in activating the immune responses was investigated by detecting serum immunoglobulin G levels. The influence of an adjuvant, imiquimod, in the transcutaneous immunization was also tested.Results: Two flexible liposomes with well-encapsulated OVA were successfully prepared by film-dispersion or reverse-phase evaporation methods. The sizes of the prepared flexible liposomes ranged from 200 to 400 nm. In vivo, the fluorescence-labeled liposome was detected in hair-follicle ducts, indicating that the flexible liposome can penetrate the skin barrier through the hair follicles. Upon transcutaneous administration, the OVA-encapsulated flexible liposome elicited a strong immune response similar to that of positive control (ie, OVA solution administrated by subcutaneous injection with Al(OH)3 as an adjuvant). Co-administration of imiquimod with the OVA-loaded liposome expressed a significant enhancement on the transcutaneous immune responses.Conclusion: Results of this study highlight the nanoscale formulation, flexible liposome, as a promising carrier for the transcutaneous delivery of antigen proteins. Imiquimod was shown to be an effective adjuvant as a transcutaneous immunization enhancer with the potential for transcutaneous vaccine development.Keywords: flexible liposome, transcutaneous vaccine, immunization enhancement, adjuvant
format	article
author	Li N Peng LH Chen X Nakagawa S Gao JQ
author_facet	Li N Peng LH Chen X Nakagawa S Gao JQ
author_sort	Li N
title	Effective transcutaneous immunization by antigen-loaded flexible liposome in vivo
title_short	Effective transcutaneous immunization by antigen-loaded flexible liposome in vivo
title_full	Effective transcutaneous immunization by antigen-loaded flexible liposome in vivo
title_fullStr	Effective transcutaneous immunization by antigen-loaded flexible liposome in vivo
title_full_unstemmed	Effective transcutaneous immunization by antigen-loaded flexible liposome in vivo
title_sort	effective transcutaneous immunization by antigen-loaded flexible liposome in vivo
publisher	Dove Medical Press
publishDate	2011
url	https://doaj.org/article/2bd338036757493d9fbc2131652e63dd
work_keys_str_mv	AT lin effectivetranscutaneousimmunizationbyantigenloadedflexibleliposomeinvivo AT penglh effectivetranscutaneousimmunizationbyantigenloadedflexibleliposomeinvivo AT chenx effectivetranscutaneousimmunizationbyantigenloadedflexibleliposomeinvivo AT nakagawas effectivetranscutaneousimmunizationbyantigenloadedflexibleliposomeinvivo AT gaojq effectivetranscutaneousimmunizationbyantigenloadedflexibleliposomeinvivo
_version_	1718399447296114688

Effective transcutaneous immunization by antigen-loaded flexible liposome in vivo

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