D-Lin-MC3-DMA [1224606-06-7]

Katalog-Nummer HY-112251-25mg

Size : 25mg

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D-Lin-MC3-DMA, an ionizable cationic lipid, is a potent siRNA delivery vehicle.

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D-Lin-MC3-DMA Chemische Struktur

CAS. Nr. : 1224606-06-7

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  • Biologische Aktivität

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D-Lin-MC3-DMA, an ionizable cationic lipid, is a potent siRNA delivery vehicle.

In Vitro

Preparation of MC3 Lipid Nanoparticles

Here we provide lipid molar ratios for LNPs in FDA-approved Patisiran (a siRNA targets the transthyretin (TTR) mRNA). The molar ratio of lipids in this formulation is D-Lin-MC3-DMA : DSPC : Cholesterol : PEG2000-C-DMG = 50 : 10 : 38.5 : 1.5, and RNA to lipid weight ratio is 0.05 (wt/wt).

A. Lipid Mixture Preparation

1. Dissolve lipids in ethanol and prepare 10 mg/m stock solutions. The lipid stock solutions can be stored at −20°C for later use.

Note 1: The ionizable lipid is usually a liquid. Due to the viscosity, it should always be weighed rather than relying on the autopipette volume.

Note 2: Cholesterol in solution should be kept warm (>37℃) to maintain fluidity. Transfer the cholesterol solution promptly to avoid cooling.

2. Prepare the lipid mixture solution as described. For each mL of lipid mixture add the following: 548 µL of 10mg/mL D-Lin-MC3-DMA (HY-112251), 254 µL of 10mg/mL Cholesterol (HY-N0322), 134 µL of 10mg/mL DSPC (HY-W040193), and 64 µL of PEG2000-C-DMG (HY-145411) . Mix the solutions thoroµghly to achieve a clear solution. This mixture contains 10 mg of total lipid.

Note 3: The choice of lipids and ratios may be changed as desired and this will affect the LNP properties (size, polydispersity, and efficacy) and the amount of mRNA required.

B. siRNA Preparation

1. Prepare a 166.7 µg/mL siRNA solution with 100 mM pH 5 sodium acetate buffer.

Note 4: The lipid:siRNA weight ratio influences the encapsulation efficiency. Other weight ratios may be prepared as alternative formulations and should be adjusted accordingly by user.

C. Mixing

There are three commonly used methods to achieve rapid mixing of the solutions: the pipette mixing method, the vortex mixing method, and the microfluidic mixing method. All these mixing methods can be used for various applications.

It is important to note that pipette mixing method and vortex mixing method may yield more heterogeneous LNPs with lower encapsulation efficiencies and is prone to variability. Microfluidic devices enable rapid mixing in a highly controllable, reproducible manner that achieves homogeneous LNPs and high encapsulation efficiency. Within these devices, the ethanolic lipid mixture and aqueous solution are rapidly combined in individual streams. LNPs are formed as the two streams mix and are then collected into a single collection tube.

1. Pipette Mixing Method:

1.1. Pipette 3 mL of the siRNA solution and quickly add it into 1 mL of the lipid mixture solution (A 1:3 ratio of ethanolic lipid mixture to aqueous buffer is generally used.) Pipette up and down rapidly for 20–30 seconds.

1.2. Incubate the resulting solution at room temperature for up to 15 minutes.

1.3. After mixing, the LNPs were dialyzed against PBS (pH 7.4) for 2 h, sterile filtered using 0.2 μm filters, and stored at 4°C.

2. Vortex Mixing Method:

1.1. Vortex 3 mL of siRNA solution at a moderate speed on the vortex mixer. Then, Quickly add 1 mL of the lipid mixture solution into the vortexing solution (A 1:3 ratio of ethanolic lipid mixture to aqueous buffer is generally used.). Continue vortexing the resulting dispersion for another 20–30 seconds.

1.2. Incubate the resulting solution at room temperature for up to 15 minutes.

1.3. After mixing, the LNPs were dialyzed against PBS (pH 7.4) for 2 h, sterile filtered using 0.2 μm filters, and stored at 4°C.

3. Microfluidic Mixing Method:

1.1 The 3 mL of siRNA buffer solution and 1 mL of the lipid mixture solution were mixed at a total flow rate of 12  mL/min (A 1:3 ratio of ethanolic lipid mixture to aqueous buffer is generally used.) in a microfluidic device.

Note 5: Parameters such as the flow rate ratio and total flow rate can be altered to fine-tune LNPs.

1.2. After mixing, the LNPs were dialyzed against PBS (pH 7.4) for 2 h, sterile filtered using 0.2 μm filters, and stored at 4°C.

Reference

1. Curr Issues Mol Biol. 2022 Oct 19;44(10):5013-5027.

2. Curr Protoc. 2023;3(9):e898.

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

Lipid nanoparticles (LNPs) containing distearoylphosphatidlycholine (DSPC), and ionizableamino-lipids such as dilinoleylmethyl-4-dimethylaminobutyrate (DLin-MC3-DMA) are potent siRNA delivery vehicles in vivo. LNP-siRNA systems optimize to achieve maximum gene silencing potency in hepatocytesfollowing IV administration in mice contain DLin-MC3-DMA (MC3), DSPC, cholesterol and a polyethyleneglycol (PEG)-lipid at mole ratios of 50/10/38.5/1.5. DLin-MC3-DMA exhibits an optimized pKa value that leads to dramatically enhanced potency.

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

642.09

C43H79NO2

1224606-06-7

Liquid

Colorless to light yellow

O=C(OC(CCCCCCCC/C=C\C/C=C\CCCCC)CCCCCCCC/C=C\C/C=C\CCCCC)CCCN(C)C

Room temperature in continental US; may vary elsewhere.

In Vitro: 

Ethanol : 125 mg/mL (194.68 mM; Need ultrasonic)

DMSO : 100 mg/mL (155.74 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 1.5574 mL 7.7871 mL 15.5741 mL
5 mM 0.3115 mL 1.5574 mL 3.1148 mL
10 mM 0.1557 mL 0.7787 mL 1.5574 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

  • Molaritätsrechner

  • Verdünnungsrechner

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass
=
Concentration
×
Volume
×
Molecular Weight *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

×
Volume (start)

V1

=
Concentration (final)

C2

×
Volume (final)

V2

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

    Add each solvent one by one:  10% DMSO    90% Saline

    Solubility: 6.25 mg/mL (9.73 mM); Suspended solution; Need ultrasonic

  • Protocol 2

    Add each solvent one by one:  5% DMSO    40% PEG300    5% Tween-80    50% Saline

    Solubility: 5 mg/mL (7.79 mM); Suspended solution; Need ultrasonic

  • Protocol 3

    Add each solvent one by one:  5% DMSO    95% (20% SBE-β-CD in Saline)

    Solubility: 5 mg/mL (7.79 mM); Suspended solution; Need ultrasonic

  • Protocol 4

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

    Solubility: ≥ 2.5 mg/mL (3.89 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

    Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
  • Protocol 5

    Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in Saline)

    Solubility: 2.5 mg/mL (3.89 mM); Suspended solution; Need ultrasonic

    This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

    Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
  • Protocol 6

    Add each solvent one by one:  10% DMSO    90% Corn Oil

    Solubility: ≥ 2.5 mg/mL (3.89 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

  • Protocol 7

    Add each solvent one by one:  10% DMSO    90% Corn Oil

    Solubility: ≥ 2.5 mg/mL (3.89 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

g

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO +
+
%
Tween-80 +
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
  • [1]. Kulkarni JA, et al. Design of lipid nanoparticles for in vitro and in vivo delivery of plasmid DNA. Nanomedicine. 2017 May;13(4):1377-1387.  [Content Brief]

    [2]. Ferraresso F, Strilchuk AW, Juang LJ, Poole LG, Luyendyk JP, Kastrup CJ. Comparison of DLin-MC3-DMA and ALC-0315 for siRNA Delivery to Hepatocytes and Hepatic Stellate Cells. Mol Pharm. 2022;19(7):2175-2182.  [Content Brief]

  • [1]. Kulkarni JA, et al. Design of lipid nanoparticles for in vitro and in vivo delivery of plasmid DNA. Nanomedicine. 2017 May;13(4):1377-1387.

    [2]. Ferraresso F, Strilchuk AW, Juang LJ, Poole LG, Luyendyk JP, Kastrup CJ. Comparison of DLin-MC3-DMA and ALC-0315 for siRNA Delivery to Hepatocytes and Hepatic Stellate Cells. Mol Pharm. 2022;19(7):2175-2182.

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO / Ethanol 1 mM 1.5574 mL 7.7871 mL 15.5741 mL 38.9354 mL
5 mM 0.3115 mL 1.5574 mL 3.1148 mL 7.7871 mL
10 mM 0.1557 mL 0.7787 mL 1.5574 mL 3.8935 mL
15 mM 0.1038 mL 0.5191 mL 1.0383 mL 2.5957 mL
20 mM 0.0779 mL 0.3894 mL 0.7787 mL 1.9468 mL
25 mM 0.0623 mL 0.3115 mL 0.6230 mL 1.5574 mL
30 mM 0.0519 mL 0.2596 mL 0.5191 mL 1.2978 mL
40 mM 0.0389 mL 0.1947 mL 0.3894 mL 0.9734 mL
50 mM 0.0311 mL 0.1557 mL 0.3115 mL 0.7787 mL
60 mM 0.0260 mL 0.1298 mL 0.2596 mL 0.6489 mL
80 mM 0.0195 mL 0.0973 mL 0.1947 mL 0.4867 mL
100 mM 0.0156 mL 0.0779 mL 0.1557 mL 0.3894 mL
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  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

D-Lin-MC3-DMA1224606-06-7LiposomeInhibitorinhibitorinhibit

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Produktname:
D-Lin-MC3-DMA
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HY-112251
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