Cationic phospholipid-polymer hybridized nanoparticle vaccine adjuvant of common-carrier antigen, MPLA (Monophosphoryl Lipid A) and IMQ (Imiquimod) as well as preparation method and application thereof

A vaccine adjuvant and cationic technology, which is applied in the field of cationic phospholipid-polymer hybrid nanoparticle vaccine adjuvant and preparation, can solve the problems of low drug loading, low biocompatibility, and rapid drug leakage, so as to promote DCs Mature, good adjuvant effect, effect of improving antigen uptake

Active Publication Date: 2018-11-06
INST OF BIOMEDICAL ENG CHINESE ACAD OF MEDICAL SCI
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, liposomes have disadvantages such as low drug loading and rapid drug leakage, and polymer nanoparticles have lower b

Method used

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  • Cationic phospholipid-polymer hybridized nanoparticle vaccine adjuvant of common-carrier antigen, MPLA (Monophosphoryl Lipid A) and IMQ (Imiquimod) as well as preparation method and application thereof
  • Cationic phospholipid-polymer hybridized nanoparticle vaccine adjuvant of common-carrier antigen, MPLA (Monophosphoryl Lipid A) and IMQ (Imiquimod) as well as preparation method and application thereof
  • Cationic phospholipid-polymer hybridized nanoparticle vaccine adjuvant of common-carrier antigen, MPLA (Monophosphoryl Lipid A) and IMQ (Imiquimod) as well as preparation method and application thereof

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preparation example Construction

[0034] The invention provides a preparation method of an antigen-loaded cationic phospholipid-polymer hybrid nanoparticle vaccine adjuvant, comprising the steps of:

[0035] S1: Dissolve the amphiphilic triblock copolymer PCL-b-PEG-b-PCL and the cationic phospholipid DOTAP in an organic solvent, then remove the organic solvent by rotary evaporation, and form a uniform film on the bottle wall, blow with nitrogen Dry the residual solvent, then put it in a vacuum drying oven, and dry it in vacuum for 12-24h; wherein, the molecular weight of the amphiphilic triblock copolymer PCL-b-PEG-b-PCL is 10000-24000, preferably 16000, wherein PEG The mass percentage of the hydrophilic segment is greater than 45%, the mass ratio of the amphiphilic triblock copolymer PCL-b-PEG-b-PCL to the cationic phospholipid DOTAP is 20 mg: (0.5-2) mg; the organic solvent is selected from acetonitrile, A mixture of one or more of dichloromethane and chloroform;

[0036] Preferably, it also includes the st...

Embodiment 1

[0041] This embodiment provides a cationic phospholipid-polymer hybrid nanoparticle vaccine adjuvant loaded with antigen OVA. The preparation method comprises steps:

[0042] S1: Dissolve 20mg of amphiphilic triblock copolymer PCL-b-PEG-b-PCL and 1mg of cationic phospholipid DOTAP in dichloromethane, then remove the organic solvent by rotary evaporation, and form a uniform film on the bottle wall, Dry the residual solvent with nitrogen, then put it in a vacuum drying oven, and dry it in vacuum for 12-24 hours; among them, the molecular weight of the amphiphilic triblock copolymer PCL-b-PEG-b-PCL is 16000, and the PEG hydrophilic chain Segment mass percentage greater than 45%.

[0043] S2: Add 10 mL of double-distilled water to the dried product, hydrate at 65°C for 5 hours, oscillate and mix evenly, and then sonicate for 10 minutes in an ice bath to form a stable emulsion, filter the stable emulsion with a 0.45 μm filter membrane, collect the filtrate, and obtain Cationic pho...

Embodiment 2

[0047] This embodiment provides a cationic phospholipid-polymer hybrid nanoparticle vaccine adjuvant loaded with TLR7 agonist IMQ and antigen OVA. The preparation method includes the steps:

[0048] S1: 20 mg amphiphilic triblock copolymer PCL-b-PEG-b-PCL, 1 mg cationic phospholipid DOTAP, and 100 μg TLR7 agonist IMQ were dissolved in dichloromethane, and then the organic solvent was removed by rotary evaporation, forming a layer a uniform film, dry the residual solvent with nitrogen, put it in a vacuum drying oven, and dry it in vacuum for 12 hours; wherein, the molecular weight of the amphiphilic triblock copolymer PCL-b-PEG-b-PCL is 16000, of which PEG The mass percentage of the hydrophilic segment is greater than 45%.

[0049] S2: Add 10 mL of double-distilled water to the dried product, hydrate at 65°C for 5 hours, oscillate and mix evenly, and then sonicate for 10 minutes in an ice bath to form a stable emulsion, filter the stable emulsion with a 0.45 μm filter membrane,...

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Abstract

The invention relates to a cationic phospholipid-polymer hybridized nanoparticle vaccine adjuvant of a common-carrier antigen, MPLA (Monophosphoryl Lipid A) and IMQ (Imiquimod) as well as a preparation method and application thereof. The vaccine adjuvant is characterized in that the IMQ as a TLR7 agonist is loaded on a hydrophobic core; the MPLA as a TLR4 agonist is loaded in a phopholipid layer;cationic phospholipid DOTAP (1,2-dioleoy-3-trimethylammonium-propane) in the phopholipid layer is used for adsorbing an antigen; the antigen is protected through hybridized nanoparticles, and the ingestion of the antigen by dendritic cells is improved; immune response after antigen stimulation is improved remarkably through the TLR agonist, and cross-presentation of the antigen is improved remarkably. The hybridized nanoparticles as the vaccine adjuvant can load the antigen and different types of TLR agonists simultaneously, can deliver the antigen through a plurality of immune paths, and promotes the DC activation and maturation. The cross-presentation level is raised, a strong and powerful T-cell killing effect is achieved, cell factor secretion is induced, a long-term memory T-cell reaction is generated, and higher prevention capability for tumors is achieved.

Description

technical field [0001] The invention relates to the technical field of vaccine adjuvants, in particular to a cationic phospholipid-polymer hybrid nanoparticle vaccine adjuvant co-carrying antigens, MPLA and IMQ, as well as its preparation method and application. Background technique [0002] Vaccination is one of the most effective ways to prevent infectious diseases or fight cancer. A successful vaccine should be able to generate long-lasting humoral and cellular immune responses against a specific pathogen. Dendritic cells (DCs) are professional antigen-presenting cells (Antigen-presenting cells, APCs), which play a key role in linking innate and adaptive immune responses. After capturing and presenting antigens, DCs present them to T cells and stimulate CD8 through MHC-class I molecules + Cytotoxic T lymphocyte (CTL) response or activation of CD4 by MHC-II molecules + T cell-mediated humoral immunity. However, protein or peptide antigens in the free state are often cl...

Claims

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Application Information

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IPC IPC(8): A61K39/39A61K9/51A61K47/24A61P35/00
CPCA61K9/5123A61K39/39A61K2039/55511A61P35/00Y02A50/30
Inventor 朱敦皖张琳华务圣洁秦玉张力
Owner INST OF BIOMEDICAL ENG CHINESE ACAD OF MEDICAL SCI
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