上海交通大学学报（医学版）

上海交通大学学报（医学版） ›› 2018, Vol. 38 ›› Issue (2): 155-.doi: 10.3969/j.issn.1674-8115.2018.02.008

• 论著（基础研究） • 上一篇    下一篇

细菌外膜囊泡包覆的载药纳米粒的制备及其小鼠鼻腔免疫效果评价

胡慧冰 1，侯昕宇 1，贺牧野 1，高峰 1,2,3   

  1. 1. 华东理工大学 药学院药剂教研组，2. 上海市新药设计重点实验室，3. 上海市功能性材料化学重点实验室，上海 200237
  • 出版日期:2018-02-28 发布日期:2018-03-09
  • 通讯作者: 高 峰，电子信箱：fgao@ecust.edu.cn。
  • 作者简介:?胡慧冰（1990—），女，硕士生；电子信箱：huibing2016@126.com。
  • 基金资助:
     上海市自然科学基金（17ZR1406600）

Preparation of bacterial outer membrane vesicle coated nanoparticle loaded with drug and evaluation  of its nasal immune effect in mice

HU Hui-bing1, HOU Xin-yu1, HE Mu-ye1, GAO Feng1, 2, 3   

  1. 1. Department of Pharmaceutics, School of Pharmacy, East China University of Science and Technology, 2. Shanghai Key Laboratory of New Drug Design, 3. Shanghai Key Laboratory of Functional Materials Chemistry, Shanghai 200237, China
  • Online:2018-02-28 Published:2018-03-09
  • Supported by:
    Natural Science Foundation of Shanghai, 17ZR1406600

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摘要： 目的 · 制备细菌外膜囊泡（outer membrane vesicle，OMV）包覆的载卵清蛋白（ovalbumin，OVA）聚乳酸 - 羟基乙酸共聚
物 [poly (lactic-co-glycolic acid) copolymer，PLGA] 纳米载体并用于小鼠鼻腔免疫效果评价。方法 · 采用超滤离心法制备 OMV，采用
乳化溶剂挥发法制备包载 OVA 的 PLGA 纳米粒（nanoparticle，NP），采用机械挤出法制备 OMV 包覆的 PLGA 载药 NP，并对其进行
表征。载 OVA 的 OMV-PLGA NP 经 BALB/c 小鼠鼻腔给药，用 ELISA 法检测鼻腔灌洗液、空肠黏膜和粪便中特异性 sIgA 抗体水平。
结果 · OMV 包覆的 PLGA 载药 NP 粒径为 (234.4±22.9) nm，透射电子显微镜观察其具有核壳结构。给药 14 d 后，载 OVA 的 OMV-PLGA
NP 给药组在鼻腔灌洗液、空肠黏膜及粪便中 sIgA 抗体水平最高；与 OMV+OVA 给药组相比，载 OVA 的 OMV-PLGA NP 给药组在鼻
腔灌洗液、空肠黏膜及粪便中的 OVA 特异性 sIgA 抗体水平分别提高了 1.6、2.1 和 1.7 倍，OMV 特异性 sIgA 抗体水平均提高了 1.5 倍。
结论 · 该纳米给药系统能同时使 OMV 和 OVA 被摄取与呈递，产生较强的小鼠黏膜免疫诱导反应。

关键词: 细菌外膜囊泡, 卵清蛋白, 聚乳酸 - 羟基乙酸共聚物, 免疫, 纳米给药系统

Abstract:

] Objective · To prepare a bacterial outer membrane vesicle (OMV) coated poly (lactic-co-glycolic acid) copolymer (PLGA) nanoparticle
loaded with ovalbumin (OVA) and evaluate its intranasal immune effect in mice. Methods · OMV was prepared by ultrafiltration concentration method.
OVA loaded PLGA nanoparticle (NP) was prepared by emulsion-solvent evaporation method. OMV coated PLGA nanoparticle (OMV-PLGA NP) loaded
with OVA was prepared by extrusion method and characterized. BALB/c mice were intranasally immunized and specific sIgA levels in nasal wash,
jejunum and fecal pellet were determined by ELISA. Results · Size of OVA loaded OMV-PLGA NP was (234.4±22.9) nm. The shell-core structure of
OVA loaded OMV-PLGA NP was proved by transmission electron microscope. After 14 d of administration, sIgA antibody levels in nasal wash, jejunum
and fecal pellet of OVA loaded OMV-PLGA NP treated group were the highest in all treated groups. Compared with the group treated with OMV and
OVA, OVA-specific sIgA antibody level in nasal wash, jejunum and fecal pellet of OVA loaded OMV-PLGA NP treated group was increased 1.6, 2.1 and
1.7 times, respectively. Compared with the group treated with OMV and OVA, OMV-specific sIgA antibody level in nasal wash, jejunum and fecal pellet
of OVA loaded OMV-PLGA NP treated group was all increased 1.5 times. Conclusion · This novel nanoparticle drug delivery system can simultaneously
delivery OVA and OMV to antigen presenting cells, resulting in stronger mucosal immune response in mice.

Key words: bacterial outer membrane vesicle, ovalbumin, poly(lactic-co-glycolic acid) copolymer, immunization, nanoparticle drug delivery system