Surface assembly of Poly (I:C) on Polyethyleneimine modified Gelatin Nanoparticles as Immunostimulatory Carriers of Antigen for Mucosal Delivery

• Main Authors: Jeng-Shiang Tsai, 蔡政翔
• Other Authors: 黃義侑
• Format: Others
• Language: zh-TW
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/47917116109783463654

碩士 === 國立臺灣大學 === 醫學工程學研究所 === 104 === In the past, the vaccine has been research to attack the disease. This disease is including about the infectious disease. However, up to now the vaccine administrations are used to inject the vaccine in body. The injection owing to cause the pain, many people don’t want to accept the vaccine injection. Because of this reason, we want to use the mucosal delivery to change the disadvantage of the injection. The history of making vaccine has been used to achieve the goals which are better effective result and the safe. However, Live/attenuated vaccines have the good result but they are not safe for the patient. And the inactivated vaccine has decreased the dosage for the patient safe but it was not effective for curing the disease. We need to find the method which can decrease the dosage and have the better treatment effect. So we can use the delivery system to overcome this aim. The successful vaccine needs three important things including with antigen, delivery system and immune-stimulator. In this study, the Ovalbumin (OVA) was used to be the antigen model. The positive gelatin nanoparticles were used to be the material of delivery system. And the Poly (I: C) was used to be the immune-stimulator. Poly (I: C) and OVA were exposed on the outer surface of positive gelatin nanoparticles. The particle sizes of each positive gelatin nanoparticle with OVA and Poly (I: C) were controlled to smaller than 500nm. And the absorption of OVA at this particle has up to 95%. We demonstrated the Poly (I:C) and OVA incorporated positive gelatin nanoparticles effectively facilitated antigen uptake by mouse bone-marrow derived dendritic cells (BMDCs) and macrophage in vitro, led to higher expression of maturation markers, including CD80&86, and induced higher production of pro-inflammatory cytokine. In vivo use the C57BL/6 mice and the immunization procedure was repeated 2times at 2 weeks interval. C57BL/6 mice immunized by intranasal with the Poly (I: C) and OVA incorporated positive gelatin nanoparticles produced high levels of OVA-specific IgG antibodies in their serum and secretory-IgA (s-IgA) in nasal wash fluid. Spleen cells from mice receiving the Poly (I: C) and OVA incorporated positive gelatin nanoparticles were re-stimulated with OVA and showed significantly augmented levels of IFN-γ. In addition, intranasal administration of the Poly (I: C) and OVA incorporated positive gelatin nanoparticles resulted in complete protection against EG7 tumor challenge in C57BL/6 mice. Taken together, these results indicate that nasal administration of the Poly (I: C) and OVA incorporated positive gelatin nanoparticles mediates the development of an effective immunity against tumors and might be useful for further clinical anti-tumor application.