| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
None (excipient). Lipid 8 is an ionizable cationic lipid with a pKa in the range of ∼6.5-6.8, optimal for endosomal escape. It complexes with RNA at acidic pH and facilitates delivery of nucleic acids into the cytoplasm, primarily targeting hepatocytes.
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| ln Vitro |
Lipid 8 LNPs efficiently encapsulate siRNA and mRNA (>90%). In vitro, Lipid 8 LNPs transfect HEK293 or HepG2 cells with high efficiency. For siRNA delivery, target gene knockdown (e.g., luciferase, GFP) exceeds 80% at siRNA concentrations of 0.1-10 nM. For mRNA delivery, reporter gene expression (luciferase) is robust and dose-dependent. Lipid 8 LNPs show low cytotoxicity (cell viability >85%).
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| ln Vivo |
In vivo, Lipid 8 LNPs are used for systemic delivery of RNA to the liver. Following intravenous administration, LNPs accumulate in the liver and mediate efficient gene silencing or protein expression. For example, Lipid 8 LNPs encapsulating siRNA against TTR reduce serum TTR levels by >80% after a single dose. The lipid is biodegradable, leading to rapid clearance and reduced toxicity.
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| Enzyme Assay |
Lipid 8 (information from reference, specific formula not provided) is dissolved in ethanol and mixed with helper lipids (e.g., DSPC, cholesterol, PEG2000-DMG) at optimized molar ratios (e.g., 50:10:38.5:1.5). The mixture is combined with an acidic aqueous buffer (25-50 mM sodium acetate, pH 4-5) containing nucleic acid via microfluidic mixing (flow rate ratio 3:1). LNPs (size 50-150 nm) form spontaneously. Ethanol is removed by dialysis, and pH is raised to 7.4. Encapsulation efficiency (>90%) is measured by Ribogreen assay. pKa is measured using TNS fluorescence. Particle size, PDI, and zeta potential are characterized by DLS.
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| Cell Assay |
For in vitro studies, LNPs are diluted in serum-free medium. HEK293 or HepG2 cells are seeded in 96-well plates (1-2×10⁴ cells/well) and treated with Lipid 8 LNPs at siRNA concentrations of 0.1-100 nM or mRNA doses of 0.01-1 ug/well. After 4-6 h, medium is replaced. For siRNA: target gene knockdown is assessed 24-72 h post-transfection by qRT-PCR or Western blot. For mRNA: luciferase activity is measured 24 h post-transfection. Cellular uptake is assessed by fluorescently labeled RNA via flow cytometry. Cytotoxicity is evaluated by MTT or CellTiter-Glo assay.
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| Animal Protocol |
For in vivo studies, Lipid 8 LNPs are administered intravenously via the tail vein to 6-8 week old female BALB/c or C57BL/6 mice at RNA doses of 0.1-1 mg/kg. For siRNA delivery: serum levels of target protein (e.g., TTR, ApoB, PCSK9) are measured by ELISA at 24-72 h, and mRNA levels in the liver are quantified by qRT-PCR. For mRNA delivery: bioluminescence imaging is performed 6-24 h post-dose. For biodistribution: organs (liver, spleen, kidney, lung) are harvested 24-72 h post-dose, and RNA levels are quantified by qRT-PCR. Liver function is assessed by serum ALT/AST measurement.
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| ADME/Pharmacokinetics |
Following i.v. administration, Lipid 8 LNPs have a circulation half-life of ∼2-4 h. LNPs accumulate in the liver (∼50-70% of injected dose) and spleen (∼10-20%). Lipid 8 is biodegradable; it contains ester linkages that are hydrolyzed in vivo, promoting clearance. The pKa (∼6.5-6.8) enables efficient endosomal escape. Cmax occurs within 5-30 minutes. RNA is rapidly released from the LNP after endosomal escape. No detailed PK data for Lipid 8 is publicly available.
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| Toxicity/Toxicokinetics |
Lipid 8 LNPs are generally well-tolerated at therapeutic RNA doses (0.2-1 mg/kg i.v.). Mild, transient elevation of ALT/AST may occur, returning to baseline within 48-72 h. No significant histopathological changes have been reported. Cytokine levels (IL-6, TNF-alpha) may be transiently elevated. Lipid 8 is biodegradable, which reduces the risk of accumulation and chronic toxicity. No overt toxicity (e.g., changes in body weight, behavior, or serum biomarkers) has been reported at therapeutic doses.
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| References | |
| Additional Infomation |
Lipid 8 (CAS 2226547-25-5) is an ionizable cationic lipid for research use only. No clinical trials or regulatory approvals have been reported. It belongs to a family of biodegradable ionizable lipids (including Lipid 5, Lipid 8, Lipid 9) optimized for RNA delivery. The exact chemical structure and molecular weight are disclosed in the patent literature. Lipid 8 may be used for siRNA, mRNA, and CRISPR-Cas9 delivery applications.
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| Molecular Formula |
C44H82N2O2
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|---|---|
| Molecular Weight |
671.13
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| Exact Mass |
670.637
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| CAS # |
2226547-25-5
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| PubChem CID |
139508899
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| Appearance |
Colorless to light yellow liquid
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| LogP |
14.9
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
38
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| Heavy Atom Count |
48
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| Complexity |
722
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCCCC/C=C\C/C=C\CCCCCCCCN(CCOC(=O)CCCN(C)C)CCCCCCCC/C=C\C/C=C\CCCCC
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| InChi Key |
VXHLVEWQGUIWMM-KWXKLSQISA-N
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| InChi Code |
InChI=1S/C44H82N2O2/c1-5-7-9-11-13-15-17-19-21-23-25-27-29-31-33-35-40-46(42-43-48-44(47)38-37-39-45(3)4)41-36-34-32-30-28-26-24-22-20-18-16-14-12-10-8-6-2/h13-16,19-22H,5-12,17-18,23-43H2,1-4H3/b15-13-,16-14-,21-19-,22-20-
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| Chemical Name |
2-[bis[(9Z,12Z)-octadeca-9,12-dienyl]amino]ethyl 4-(dimethylamino)butanoate
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 100 mg/mL (149.00 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.73 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (3.73 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (3.73 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.4900 mL | 7.4501 mL | 14.9002 mL | |
| 5 mM | 0.2980 mL | 1.4900 mL | 2.9800 mL | |
| 10 mM | 0.1490 mL | 0.7450 mL | 1.4900 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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