Nano aluminum-encapsulating carrier and application thereof

A nano-aluminum and carrier technology, which is applied to the carrier and its application field in vaccine adjuvant delivery systems, can solve the problems of complex preparation process, low safety, redness and swelling of the inoculation site, etc., and achieves good biocompatibility and safety. High, safety-enhancing effect

Inactive Publication Date: 2014-09-24
ANHUI MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] (3) RNA / DNA vaccine RNA / DNA vaccine is to clone the expression gene of protein antigen on the expression vector and inject it into the body so that the antigen can be expressed in the body to stimulate the body to produce an immune response. The preparation process is complicated and the safety is low.
Traditional aluminum adjuvants are mainly aluminum salts (such as aluminum sulfate, aluminum phosphate) or aluminum hydroxide coarse particles, which can easily cause adverse reactions such as redness and swelling at the inoculation site

Method used

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  • Nano aluminum-encapsulating carrier and application thereof

Examples

Experimental program
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preparation example Construction

[0038] The preparation method of the carrier of encapsulating nano-aluminum is to encapsulate the nano-aluminum inside the carrier by various methods: or simultaneously form nano-aluminum and the carrier of encapsulating nano-aluminum during the preparation of the carrier; or prepare and form encapsulating aluminum ions ( Al 3+ ) carrier, and then precipitate the encapsulated aluminum ions to form a carrier for encapsulating nano-aluminum; or prepare nano-aluminum first, and then encapsulate it in a carrier to form a carrier for encapsulating nano-aluminum.

[0039] In order to improve the encapsulation efficiency of the vaccine to be encapsulated, reduce the liposome particle size, increase stability or enhance immune activity, an appropriate amount of charged lipids, such as N-[1-(2,3-diole Acyloxy)propyl]-N,N,N-trimethylaminomethyl sulfate (DOTAP), stearylamine (SA), phosphatidylserine (PS), etc.

[0040] In order to enhance the efficacy of the vaccine, the carrier of enca...

Embodiment 1

[0045]

[0046] With OVA and 100mM AlCl 3 The solution is an aqueous phase, with EPC / LA / SA (20:0.1:1, mole ratio) as the membrane material, total lipid / OVA (10:1, mass ratio) by thin film dispersion-extrusion method (through 100nm pore membrane) Preparation of liposomes; removal of free OVA and AlCl by dextran Sephadex G-50 gel column 3 ; The liposomes were incubated with 0.5M ammonia water for 30 minutes to increase the internal pH of the liposomes; then the ammonia was removed by passing nitrogen gas to form NACs loaded with OVA liposomes. Electron microscope observation shows that NACs are monolayer and oligolamellar liposomes, which contain nano-aluminum with a particle size of 30-60 nanometers; the average particle size detected by DLS is 230 nanometers, the zeta potential is 3mV, and the encapsulation efficiency is about 35%. In vitro experiments showed that immune cells efficiently internalized liposome-constructed aluminum nanoparticles (NACs). The mice were vaccin...

Embodiment 2

[0048]

[0049] With 0.5mL100mM AlCl 3 The solution is the water phase, and 2.5 mL of SPC cyclohexane (cyclohexane) is dissolved in the oil phase, and the water phase and the oil phase (1:5, v / v) are mixed, and microemulsion A is prepared by ultrasonic emulsification. With 0.5mL100mMNa 3 PO 4 The solution is the water phase, with 2.5 mL of SPC / DOPA / MPC / MPLA (10:10:1:0.1, moleratio) cyclohexane dissolved in the oil phase, and the water phase is mixed with the oil phase (1:5, v / v) , Microemulsion B prepared by phacoemulsification. Mix microemulsions A and B for 40 minutes, add 10 mL of 5% sucrose / OVA (OVA: total fat = 10:1, w / w) aqueous solution, emulsify to form W1 / O / W2 double emulsion, freeze-dry to remove solvent; freeze-dried product Hydration, that is, the formation of loaded OVA-NACs. Electron microscope observation shows that NACs are monolayer and oligolamellar liposomes encapsulating aluminum with a particle size of 20-80 nanometers; the average particle size dete...

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Abstract

The invention discloses a nano aluminum-encapsulating carrier and an application of the nano aluminum-encapsulating carrier in constructing a vaccine adjuvant transfer system. The nano aluminum is nanoparticles of aluminum phosphate, aluminum sulfate and aluminum hydroxide or a mixture of aluminum phosphate, aluminum sulfate and aluminum hydroxide, wherein the grain size is below 1 mu m; the carrier is a lipidosome, a lipoid, an emulsion, a nano-capsule or a micro-capsule. Construction of the vaccine adjuvant transfer system is the main purpose of the nano aluminum-encapsulating carrier. The application of the nano aluminum-encapsulating carrier in constructing the vaccine adjuvant transfer system comprises the following step: encapsulating vaccine components in the nano aluminum-encapsulating carrier; or adsorbing the vaccine components on the surface of the carrier; or purely mixing with the carrier to exert the vaccine adjuvant and the transfer function. The nano aluminum-encapsulating carrier disclosed by the invention has the advantages that the nano aluminum-encapsulating carrier is wide in application range, so that the nano aluminum-encapsulating carrier is suitable for antigens with different pathogens; the nano aluminum-encapsulating carrier is high in stability and can encapsulate antigens so as to enhance in vivo and in vitro stability; the nano aluminum-encapsulating carrier is high in safety, and the use materials have good biocompatibility; the nano aluminum-encapsulating carrier is many in inoculation and wide in way, and the carrier can be inoculated through track mucosa or subcutaneous, intracutaneous and intramuscular injection; the carrier is strong in immunosuppression induction potency.

Description

technical field [0001] The invention relates to the field of vaccine preparations for preventing infectious diseases, and relates to a carrier encapsulating nano-aluminum and its application in a vaccine adjuvant delivery system. In particular, the constructed vaccine adjuvant delivery system can improve the efficiency of vaccine delivery and immune induction. Background technique [0002] Vaccines are immunogenic substances capable of producing antibodies and are preparations used to prevent infectious diseases. After years of development, the current vaccines mainly include the following types in terms of sources: [0003] (1) Inactivated vaccines are made from bacteria, viruses, rickettsia, spirochetes, etc. with good immunogenicity, which are artificially cultivated and then killed by physical or chemical methods. Such vaccines lose their ability to reproduce but retain their immunogenicity. Inactivated vaccines cannot grow and reproduce after entering the human body, ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61K9/00A61K9/107A61K9/51A61K9/50A61K39/39A61P31/00
Inventor 王汀王宁
Owner ANHUI MEDICAL UNIV
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