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Lipid cochleate carrier based on aluminum ions

A technology of lipid volume and aluminum ions, which is applied in the field of biomedicine, can solve the problems of redness and swelling at the inoculation site, and achieve the effect of strong adjuvant function, enhanced stability and wide application range

Inactive Publication Date: 2016-09-21
ANHUI MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

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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  • Lipid cochleate carrier based on aluminum ions
  • Lipid cochleate carrier based on aluminum ions

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preparation example Construction

[0030] The preparation method of novel lipid roll carrier is to adopt negatively charged phospholipid as membrane material, prepare liposome by various methods; add aluminum ion (Al 3+ ), causing the liposome phospholipid bilayer to sweep to form a helical lipid volume ACO, which is the liposome fusion method. Different phospholipids are used as membrane materials, or different preparation processes are used, resulting in different ACO particle sizes.

[0031] To enhance vaccine efficacy, ACO is further encapsulated or combined with other immune adjuvants, such as lipid A (lipid A), monophospholipid A, CpG-ODN, saponin, squalene, imiquimod, etc.; In order to improve the efficiency of vaccine delivery, the surface of ACO is modified with the corresponding ligand of APC receptor, for example, ACO is modified with mannose group.

[0032] ACO products are in the form of carrier aqueous solution; in order to improve stability, anhydrous products are further prepared by spray dryin...

Embodiment 1

[0035] Preparation of Encapsulated Antigen ACO Vaccine by Liposome Fusion Method

[0036]Use OVA (model antigen) solution as the water phase, SPS / MPLA (50:1, mole ratio, SPS concentration 1% (g / mL)) as the membrane material, SPS / OVA (20:1, mass ratio), and Thin-film dispersion-extrusion method (passing through 100 nm porous membrane) to prepare 100 nm liposomes; add 20 mM AlCl 3 solution, the liposomes fuse to form a new type of lipid volume ACO. Microscopic observation shows that ACO is a rod-shaped particle. The average particle size detected by DLS is 960 nm, the zeta potential is 20 mV, and the encapsulation efficiency is about 95%. In vitro experiments showed that mouse myeloid dendritic cells (BMDCs) efficiently internalized fluorescently labeled ACO. Mice were inoculated intramuscularly with OVA-ACO (inoculation dose 5 µg), compared with the control group (Ca 2+ Compared with traditional lipid volume group and aluminum salt adjuvant group), higher levels of INF-γ, OV...

Embodiment 2

[0039] Mannose-modified ACO vaccine prepared by emulsification and freeze-drying

[0040] Using 2.5 mL of 5% sucrose as the water phase and 0.5 mL of SPC cyclohexane (cyclohexane) as the oil phase, the water phase and the oil phase (5:1, v / v) were mixed and ultrasonically emulsified to prepare microemulsions; then frozen Dry, remove solvent; freeze-dried product with AlCl 3 Solution hydration (SPS / Al 3+ = 1:5, mol / mol), that is, the formation of ACO; followed by OVA, mannose-PEG2000-DSPE (MPE) (SPS / OVA = 20:1, mass ratio, SPS / MPE = 50:1, mole ratio,) Mix and incubate at 40 °C for 0.5h to form mannose-modified lipid rolls (MACO, mannose-modified ACO). Microscopic observation shows that MACO is a rod-shaped lipid roll with a particle size of 550 nanometers; the average particle size detected by DLS is 620 nanometers, the zeta potential is 15 mV, and the encapsulation efficiency is about 95%. In vitro experiments showed that immune cells BMDC uptake MACO in the form of recept...

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Abstract

The invention discloses a lipid cochleate carrier based on aluminum ions. ACO is mainly used as a vaccine carrier and has the strong adjuvant function, so that a vaccine adjuvant / transfer system is formed, and immunity induction potency is improved. Being used as the vaccine carrier, the lipid cochleate carrier has the obvious advantages, the ACO carrier is wide in application range, applicable to carrying different vaccines such as subunit vaccine antigen, inactivated / attenuated vaccines and DNA vaccines, ACO stability is high, meanwhile, vaccine interior and exterior stability can be improved by packaging the vaccine, safety is high, materials adopted for ACO have good biocompatibility, dosage amount is large, multiple dosage ways are provided, dosage can be achieved through sinus tract mucosa comprising oral administration and inoculation and can also be achieved through subcutaneous, intracutaneous and muscle injection, immune induction validity is strong, and ACO has the adjuvant function, and can increase cell uptake and improve immune induction validity when carrying vaccines.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, in particular to a novel lipid coil (ACO) used as a vaccine carrier. Using trivalent aluminum ions (Al 3+ ) mediates negatively charged phospholipids to sweep to form a new type of lipid coil (ACO), which is used as a vaccine carrier to exert adjuvant and delivery functions, form a vaccine adjuvant-delivery system (VADS), and improve vaccine safety, stability and efficacy. Background technique [0002] Vaccines are antigen preparations that can induce the body to eliminate pathogens, and mainly include two types: attenuated / inactivated whole pathogens; subunit vaccines, antigens / antigen-encoding DNA or RNA. Attenuated / inactivated vaccines are more effective but less safe; subunit vaccines are safer but less effective. In addition, due to factors such as pathogen biodiversity and genetic variation, some diseases lack effective vaccines, and some originally effective vaccines are less effecti...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/39A61K9/127A61K47/24A61K9/19A61K39/29
CPCA61K9/1274A61K9/1277A61K9/19A61K39/39A61K47/24A61K2039/55505C12N2730/10134
Inventor 王汀王宁
Owner ANHUI MEDICAL UNIV
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