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Protein or nucleic acid drug liposome preparation and preparation method thereof based on tetraether lipid

A technology of liposome preparation and nucleic acid drug, which is applied in the directions of liposome delivery, peptide/protein composition, pharmaceutical formulation, etc., can solve the problems of instability of common phospholipid liposomes, and achieves improved bioavailability and protection stability. , improve the efficacy of the drug

Inactive Publication Date: 2010-06-23
SHANGHAI JIAO TONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

) also discloses the application of common liposomes as vaccine oral delivery carriers, but one of the major obstacles still faces is exactly: common phospholipid liposomes are extremely unstable under the influence of bile salts in the intestinal tract

Method used

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  • Protein or nucleic acid drug liposome preparation and preparation method thereof based on tetraether lipid
  • Protein or nucleic acid drug liposome preparation and preparation method thereof based on tetraether lipid
  • Protein or nucleic acid drug liposome preparation and preparation method thereof based on tetraether lipid

Examples

Experimental program
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Effect test

Embodiment 1

[0020] Culturing of Archaea and Extraction and Purification of Tetraether Lipids

[0021] The archaea S. acidocaldarius was inoculated in the ATCC1733 culture solution, pH 2.5, placed in a 65°C bacterial incubator, and the growth of the archaea was monitored by a UV spectrophotometer at 420nm and 540nm respectively. When the archaea grew to logarithmic During the period, it was collected by centrifugation (8800rpm, 10min), and the collected bacterial solution was repeatedly frozen and thawed 3 times at -70-30°C for the extraction of tetraether lipids for later use.

[0022] Suspend the extracted lipids with chloroform: methanol: water = 1:2:0.8 for 12 hours, then add an appropriate amount of chloroform to the suspension to adjust the ratio of chloroform: methanol: water to 2:2:0.8, and continue to suspend After 12 hours, centrifuge (1800rpm, 6min) to obtain an organic phase containing lipids. After filtering to remove impurities, use methanol: water (1:1) to sonicate and apply...

Embodiment 2

[0025] Preparation of blank tetraether liposomes

[0026] Take an appropriate amount of PLFE stock solution, add it to a 50mL pear-shaped bottle, then add 6mL chloroform / methanol (2:1) and mix evenly. A uniform and transparent lipid film was formed on the wall of the bottle, and the chloroform and methanol were fully evaporated by filling with nitrogen. According to the appropriate lipid concentration, PBS aqueous solution was added to the pear-shaped bottle for hydration, and the liposomes obtained by ultrasound were measured by Zetasizer 3000HS laser diffraction particle size analyzer (PCS) for particle size distribution, average particle size and Zeta potential. The results showed that the particle size of the blank tetraether liposome was 235.6±12.3nm, the distribution was uniform, the polyindex was less than 0.3, and the surface charge was about -35.1mV.

[0027] Stability analysis of tetraether liposomes:

[0028] Using PLFE as the lipid raw material, the liposome part...

Embodiment 3

[0031] Oral administration effect of insulin tetraether liposome preparation

[0032] PLFE is a lipid material, which is hydrated with PBS aqueous solution containing insulin (insulin, 17.5IU / mL) to prepare tetraether liposomes containing protein drugs. The particle size is 268.9±4.8nm, the distribution is uniform, and the polyindex< 0.5, the encapsulation rate is about 20%. 20 diabetic model mice were fasted for 12 hours and randomly divided into 4 groups: the first group was administered intragastrically with insulin solution (insulin, ig) dissolved in phosphate buffer; the second group was intraperitoneally injected with insulin solution (insulin, ip) ; The third group was given conventional liposome-encapsulated insulin solution (Conventional liposomes, ig) by intragastric administration; the fourth group was given intragastric administration of tetraether liposome-encapsulated insulin solution (Archaeosomes, ig). The oral and intraperitoneal insulin concentrations were 3...

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Abstract

Disclosed are a protein or nucleic acid drug liposome preparation and a preparation method thereof based on tetraether lipid in large biological molecular drug technical field; the liposome membrane comprises the monomolecular layer of the tetraether lipid; wherein, the tetraether lipid accounts 50-100% of the total lipid mass, the protein drug or nucleic acid drug are dissolved in the water solution phase of the liposome membrane interior. The invention can be used as the oral carrier for polypeptide, protein, oligonucleotide and genetic drugs, guarantees the stability of the drugs in the gastrointestinal tract and improves the bioavailability and efficacy, wherein the polypeptide and protein drugs include insulin, human leukocyte colony growth factor, erythropoietin, human growth factor, calcitonin, exenatide, intestinal peptide hormone, thymosin, etc.; the vaccine antigen includes the antigens of various hepatitis virus, aids virus, HPV virus and herpes virus; the nucleic drugs include the plasmids of various genes, oligonucleotide molecules with various gene sequences and chemical modification structures thereof.

Description

technical field [0001] The invention relates to a pharmaceutical preparation in the technical field of biomacromolecular drugs and a preparation method thereof, in particular to a tetraether lipid-based protein or nucleic acid drug liposome preparation and a preparation method thereof. Background technique [0002] Oral administration of biomacromolecular drugs such as proteins and nucleic acids is not ideal. One of the reasons is that molecules such as polypeptides and nucleic acids are unstable in the gastrointestinal tract and are easily absorbed by the acidic environment of the gastrointestinal tract, surfactants, and Degraded by various proteases. In order to avoid polypeptide or nucleic acid drugs from being affected by the harsh environment in the gastrointestinal tract, researchers choose appropriate carriers to protect these vaccines or peptide drugs. Due to good biocompatibility and controllable size, surface charge and membrane fluidity, liposome preparations hav...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61K47/46A61K38/00A61K38/28A61K48/00
Inventor 徐宇虹李正荣
Owner SHANGHAI JIAO TONG UNIV
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