EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
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2011
·
IF 3.291
Tianyi Wang,Meijuan Zou,Haitao Jiang,Zhaoshuai Ji,Ping Gao,Gang Cheng
The purpose of this study is to develop a novel kind of adjuvant for oral vaccine delivery. In order to effectively prevent the degradation of antigens in the gastrointestinal tract and optimize the uptake for M cells, a novel kind of hydrophobic carbon nanoparticle (C1) with the size of 470 nm was synthesized by taking silica as a template and sucrose as a carbon source. Notably, there were large mesopores and macropores mainly of 40–60 nm, which made it to be excellent candidate as an antigen carrier. C1 was characterized using SEM, TEM and nitrogen adsorption. Following oral immunization with BSA loaded in C1, the IgG titer reached to a level almost equal to that of parenteral administration of antigen emulsified in Freund’s complete adjuvant (FCA). Mucosal IgA was also detected in intestinal, salivary and vaginal secretions, suggesting an effective stimulation of mucosal immune response. Besides, both T-helper 1 and T-helper 2 (Th1 or Th2) mediated responses were induced. We believe that the research will help in the design of novel vaccine adjuvant for improvement their potential on modulation of immune response.
研究领域:
生物医学工程
·
免疫学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2023
·
IF 5.9
Huifen Luo,Yiping Zhang,Chengdeng Chi,Tianxing Wang,Ling Chen,Xiaoxi Li
To improve the resistance to the harsh environment of the gastrointestinal tract (GIT) and the efficiency of specific binding and uptake by intestinal epithelial cells, the GRGDS-conjugated carboxymethyl starch (R-CMS) carrier was designed and the delivery system, which can enhance M-cell transport for bioactive proteins, was developed. FTIR, 1H NMR, and elemental analysis verified that GRGDS can be successfully introduced. CLSM results indicated that R-CMS shows good targeting ability to M cells. The formation of ovalbumin (OVA)-loaded nanocapsules was driven by hydrogen bond and electrostatic interactions between negatively charged R-CMS and positively charged starch. The nanocapsules were compact in structure and the Z-average diameter was only 158.8 ± 6.58 nm, and they were relatively stable under different storage conditions. Furthermore, only 44.03% of the loaded OVA were leaked out before the fabricated nanocapsules reached the M cells during GIT delivery and the bioaccessibility of OVA was improved because the arrived nanocapsules showed higher specific binding ability and transport efficiency to M cells. Accordingly, these findings would provide a promising pathway for the development of the oral delivery system for bioactive proteins through a starch-based material that improves the targeting and transport efficiency to M cells.
研究领域:
食品科学
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生物医学工程
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药剂学
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Hongping Wan,Yunhan Yang,Zhiwen Tu,Mingrun Tang,Bo Jing,Yumei Feng,Jiulong Xie,Huile Gao,Xu Song,Xinghong Zhao
In mucosal vaccination, the targeted delivery of antigens through M (microfold) cells is essential for initiating a robust antigen-specific immune response. In the present study, we devised a nano-delivery platform to target M cells. This platform involved coating mesoporous silica nanoparticles (MSN) with a mucoadhesive chitosan-catechol (Chic) layer, incorporating a recombinant antigen to form nanoparticles that enhance the immune response. The collagenase equivalent domain (COE) of porcine epidemic diarrhea virus (PEDV) terminated with the M cell-targeting sequence RGD (COER), was initially expressed by Escherichia coli ( E. coli ) and subsequently conjugated to the surface of MSN-Chic, forming the MSN-Chic-COER nanoparticles. MSN-Chic-COER with strong mucoadhesive properties and a propensity for M cell targeting, demonstrated enhanced uptake by dendritic cells (DCs) and trafficking to lymph nodes, compared to COE/COER after intranasal administration. MSN-Chic-COER recruited more dendritic cells to the antigen-located site via stimulating chemokine CCL20 secretion was evidenced by cell co-culture model. Additionally, it enhanced antigen permeability by disrupting the distribution of the ZO-1 protein in epithelial cells. Notably, MSN-Chic-COER elicited a higher level of cellular immunity, humoral immunity, and PEDV neutralizing antibody production. These findings underscore the potential of MSN-Chic-COER as a promising intranasal vaccine delivery system.
研究领域:
免疫学
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疫苗学
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生物材料科学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Lei Xie,Yiping Zhang,Ling Chen,Tianxing Wang,Shuo Zhang,Xiaoxi Li
Characterizing the structural changes of cell-targeting delivery carriers in gastrointestinal tract (GIT) is crucial for understanding their effectiveness in cell targeting and transport. Herein, RGD peptide-grafted carboxymethyl starch (CMS) and cationic quaternary ammonium starch (QAS) were utilized to fabricate quintet-layered nanocapsules loaded with ovalbumin (OVA). The aim was to improve delivery and transportation efficiency, specifically targeting M cells. The research analyzed the impact of pH and enzyme variations in GIT on the structure of nanocapsules, interactions between carriers and the release behavior of OVA. Results showed that the size of nanocapsules increased from 229.2 to 479.8 nm and the zeta potential decreased from −1.08 to −33.33 mV during oral delivery. This was evident in TEM images, showing a more relaxed core-shell structure. Isothermal titration calorimetry and molecular dynamic simulation indicated that pH changes primarily affected the electrostatic interaction between carriers. Increasing pH led to reduced affinity constants, and around 84.42 % of OVA was successfully delivered to M cells. Moreover, the transport efficiency of nanocapsules to M cells was five times greater than that of Caco-2 cells. This suggests the feasibility of developing a nanocapsules delivery system capable of adapting to pH changes in GIT by regulating electrostatic interactions between carriers.
研究领域:
食品科学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2021
·Vol. 12
·期 12
·5551-5562
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IF 5.396
Mengjie Ma,Han Wang,Yongkai Yuan,Yuanhong Wang,Shuang Yang,Zhihua Lv
The purpose of this study was to investigate the absorption and transport of glycosaminoglycan from Apostichopus japonicus (AHG) and its depolymerized derivatives (DAHG-1, DAHG-2, DAHG-3). The AHG and depolymerized AHGs (DAHGs) were characterized by high-performance gel permeation chromatography (HPGPC), Raman spectroscopy and atomic force microscopy (AFM). The results showed that there was no significant difference of an AHG primary structure and functional groups during the depolymerization. Meanwhile, AFM observation showed that AHG and DAHGs possessed linear structures. In this study, a rapid and sensitive liquid chromatographic post-column derivatization method was used to investigate the absorption of AHG and DAHGs with the Caco-2 cell model, the M cell model and the intestinal recirculating perfusion. It was found that AHG and DAHGs can be absorbed in the intestine, and their transport involved endocytosis.
研究领域:
生物化学
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药学
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营养学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Ya Zhao,Ping Li,Xiaoshuang Wang,Yayun Wu,Lijuan Liu,Ruizhi Zhao
Polysaccharides of vinegar-baked Radix Bupleuri (VBCP) have been reported to exhibit liver-targeting and immunomodulatory activities through oral administration, but the absorption behavior and mechanism of VBCPs have not been extensively studied. In this study, a novel HG type pectin polysaccharide, VBCP1–4, with a high molecular weight of 2.94 × 10 6 Da, was separated from VBCP. VBCP1–4 backbone was contained 1,4-α-D-Gal p A, 1,4-α-D-Gal p A6OMe, 1,3,4-α-D-Gal p A and 1,2,4-α-D-Rhap. The branches were mainly contained 1,5-α-L-Araf, 1,3,5-α-L-Araf, t-α-L-Araf and t-α-D-Gal p , which linked to the 3 position of 1,3,4-α-D-Gal p A and the 4 position of 1,2,4-α-D-Rha p . VBCP1–4 could self-assemble to nanoparticles in water, with CMC values of 106.41 μg/mL, particle sizes of 178.20 ± 2.82 nm and zeta potentials of −23.19 ± 1.44 mV. The pharmacokinetic study of VBCP1–4, which detected by marking with FITC, revealed that it could be partially absorbed into the body through Peyer's patches of the ileum. In vitro absorption study demonstrated that VBCP1–4 was difficult to be absorbed by Caco-2 cell monolayer, but could be absorbed by M cells in a time and concentration dependent manner. The absorption mechanism was elucidated that VBCP1–4 entered M cells through clathrin-mediated endocytosis in the form of nanoparticles. These findings provide valuable insights into the absorption behavior of VBCP and contribute to its further development.
研究领域:
药理学
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生物化学
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纳米技术
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2024
·
IF 10.7
Kaiping Wang,Yuxuan Liu,Zeming Zhang,Ziming Zheng,Wenqi Tang,Wangtianzi Teng,Xu Mu,Jinglin Wang,Yu Zhang
Lentinan (LNT), a natural polysaccharide, has been reported to exhibit immunomodulatory effects in the intestine after oral administration. Herein, we aimed to investigate the lymphatic transport of LNT in Peyer's patches (PPs) by traceable fluorescent labeling and to explore whether/how LNT contacts related immune cells. Near-infrared imaging confirmed the absorption of LNT in the small intestinal segment and its accumulation within PPs after oral administration. Subsequently, tissue imaging confirmed that M cells are the main cells responsible for transporting LNT to PPs, and an M cell model was established to explore the involvement of Dectin-1 in the absorption process. Systematic in vitro and in vivo studies revealed that the Dectin-1 further mediates the uptake of LNT by mononuclear phagocytes in PPs. Moreover, LNT can promote the proliferation and differentiation of mononuclear phagocytes, thereby activating immune responses. In summary, this study elucidates the pharmacokinetic mechanisms by which LNT exerts oral immunomodulatory effects, providing a theoretical basis for the development and application of other polysaccharides.
研究领域:
免疫学
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药理学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Hongyan Lu,Yikun Gao,Jianmin Chen,Jing Chai,Ansheng Li,Tongtong Sun,Yuling Mao,Ye He,Qinfu Zhao,Jinghai Zhang,Siling Wang
Oral vaccines hold great promise for preventing major infectious diseases, but their development is limited by various gastrointestinal tract (GIT) barriers and the low proportion of intestinal microfold (M) cells. Here, inspired by the specific absorption pathway of dietary fat, a novel bionic intestinal lymphatic delivery system based on large mesoporous silica nanoparticles (LMSN) was developed for oral delivery of H1N1 influenza split vaccine (SV). Encouragingly, LMSN with triglyceride biomimetic structure and encapsulated by double-end palmitic acid esterified PEG (PEG-DP), namely [email protected] , exhibited high intestinal epithelium permeability and excellent lymphatic targeting ability. Additionally, TGLMSN, which acting as both antigen carrier and adjuvant, significantly enhanced the ability of SV to stimulate dendritic cells maturation. The results demonstrated that [email protected] vigorously augmented SV-induced antigen-specific systemic and mucosal immunity, compared to oral SV alone. To our knowledge, this is the first study to customize mesoporous silica nanocarriers to load SV and deliver vaccines to mesenteric lymph nodes (MLNs) mainly through the intestinal epithelium cells (IECs) pathway rather than M cells route alone. This work will not only improve the existing influenza vaccination methods, but also open up a new avenue for the design of vaccines against pathogens infected via mucosal route.
研究领域:
药学
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免疫学
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纳米技术
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病毒学
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产品关联
DOI
高影响因子
ACS Nano
·
2023
·
IF 17.1
Naihan Huang,Xiao-Yan Tang,Wei Meng,Ye-Hua Lai,Xuan Zhou,Xue-Zhao Yu,Wen-Hua Zhang,Jin-Xiang Chen
Due to the immunosuppressive tumor microenvironment (TME) and weak radiation absorption, the immune response triggered by radiation therapy (RT) is limited. Herein, a core–shell nanosensitizer UiO@MnS (denoted as UM) was genuinely constructed for the amplification of RT efficacy and induction of immunogenicity via integrating MnS-reprogrammed TME with Hf-based UiO-sensitized RT. The acid-sensitive MnS would produce H2S under acidic TME to improve oxygenation through inhibition mitochondrial respiration and reducing metabolic oxygen consumption, leading to decreased HIF-1α expression and enhanced radiosensitization. In addition, the generated H2S inhibited the catalase activity to increase the H2O2 level, which subsequently enhanced the Mn2+-mediated Fenton-like reaction, resulting in G2/M cell cycle arrest to improve the cellular sensitivity for radiation. This impressive tumor oxygenation, cell cycle arrest, and radiosensitization procedure boosted RT efficacy and resulted in strong antitumor immunogenicity. Taken together, combining the immunosuppressive TME modulation with a sensitizing radiation strategy shows great promise for magnifying immunogenic RT outputs.
研究领域:
癌症研究
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纳米技术
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放射肿瘤学
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免疫治疗
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肿瘤微环境
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）