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Glyceryl Trimyristate/Trimyristin

Trimyristin (TM) is an ester with the chemical formula C45H86O6. It is a saturated fat which is the triglyceride of myristic acid. TM is a white to yellowish-gray solid that is insoluble in water, but soluble in ethanol, benzene, chloroform, dichloromethane, and ether. The solid triglyceride TM (bulk melting point 56oC) exhibits strong supercooling in the nanoparticulate state. Therefore, TM nanoparticles remain liquid after preparation by melt-homogenization and crystallize only below room temperature.

Skeletal formula of TM.Fig.1 Skeletal formula of TM.

Improving Oral Absorption of Salmon Calcitonin by TM Lipid Nanoparticles

Solid lipid nanoparticles (SLN) were prepared by w/o/w emulsion technology. The particles were composed of solid lipid TM and surfactant poloxamer 407 for oral transport of salmon calcitonin. The average particle size of TM SLN is 200 nm and the association efficiency with calcitonin is about 86%. At the dose of 500 IU / kg, SLN can reduce the basic blood calcium level by 20% and last for more than 8 hours. The results showed that the combination of salmon calcitonin and TM SLN was the key factor to improve the efficiency of oral delivery protein.

The Physical State of TM LNPs Influences Their Effect on in Vitro Cell Viability

Cryo-TEM investigations revealed the presence of differently shaped particles in the formulations. The liquid TM particles (left column) had a typical droplet shape, irrespective of the type of stabilizer.

Cryo-electron micrographs of the particle formulations.Fig.2 Cryo-electron micrographs of the particle formulations. (Petersen, 2011)

Several mechanisms can induce cytotoxicity of LNPs. One key factor might be a high particle uptake. To evaluate this potential mechanism, cell uptake studies were conducted using DiI-labelled LNPs with a TM matrix. Confocal micrographs did indeed point to relatively high uptake of all DiI-labelled TM-F68 formulations within a short time whereas the uptake of TM-Tw80 formulations was almost negligible.

Confocal laser scanning micrographs of L929 mouse fibroblasts after 2 or 24 h incubation with TM-Tw80 LNPs in the supercooled liquid (L) and the crystalline (C) state.Fig.3 Confocal laser scanning micrographs of L929 mouse fibroblasts after 2 or 24 h incubation with TM-Tw80 LNPs in the supercooled liquid (L) and the crystalline (C) state. (Petersen, 2011)

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Reference

  1. Petersen, S.; et al. The physical state of lipid nanoparticles influences their effect on in vitro cell viability. European journal of pharmaceutics and biopharmaceutics. 2011, 79(1): 150-161.
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