Protamine-based nanoparticles as new antigen delivery systems

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• 作者：José ; Vicente Gonzá ; lez-Aramundiz^a ; ^c ; ¹ ; ^{jvgonzal@uc.cl" class="auth_mail" title="E-mail the corresponding author} ; Mercedes Peleteiro Olmedo^b ; ¹ ; ^{mpeleteiro@uvigo.es" class="auth_mail" title="E-mail the corresponding author} ; Á ; frica Gonzá ; lez-Ferná ; ndez^b ; ^{africa@uvigo.es" class="auth_mail" title="E-mail the corresponding author} ; Marí ; a José ; Alonso Ferná ; ndez^a ; ^{mariaj.alonso@usc.es" class="auth_mail" title="E-mail the corresponding author} ; Noemi Stefá ; nia Csaba^a ; ^{noemi.csaba@usc.es" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Protamine sulfate (PubChem SID ; 7849283) ; Hyaluronic acid (PubChem CID ; 3084050) ; Sodium alginate (PubChem SID ; 496141)
• 刊名：European Journal of Pharmaceutics and Biopharmaceutics
• 出版年：2015
• 出版时间：November 2015
• 年：2015
• 卷：97
• 期：part_PA
• 页码：51-59
• 全文大小：1268 K

文摘

The use of biodegradable nanoparticles as antigen delivery vehicles is an attractive approach to overcome the problems associated with the use of Alum-based classical adjuvants. Herein we report, the design and development of protamine-based nanoparticles as novel antigen delivery systems, using recombinant hepatitis B surface antigen as a model viral antigen.

The nanoparticles, composed of protamine and a polysaccharide (hyaluronic acid or alginate), were obtained using a mild ionic cross-linking technique. The size and surface charge of the nanoparticles could be modulated by adjusting the ratio of the components. Prototypes with optimal physicochemical characteristics and satisfactory colloidal stability were selected for the assessment of their antigen loading capacity, antigen stability during storage and in vitro and in vivo proof-of-concept studies. In vitro studies showed that antigen-loaded nanoparticles induced the secretion of cytokines by macrophages more efficiently than the antigen in solution, thus indicating a potential adjuvant effect of the nanoparticles. Finally, in vivo studies showed the capacity of these systems to trigger efficient immune responses against the hepatitis B antigen following intramuscular administration, suggesting the potential interest of protamine–polysaccharide nanoparticles as antigen delivery systems.