Cheng_2021_J.Pharm.Sci__

Lipoprotein lipase (LPL) is an essential enzyme that hydrolyzes triglycerides in chylomicrons and very low-density lipoprotein into glycerol and fatty acids. One major hurdle in using LPL as a therapeutic has been its poor solubility/stability after purification. Solutions used to preserve purified LPL commonly contain either heparin, or concentrated glycerol and sodium chloride, resulting in hypertonic solutions. These solutions are not acceptable as pharmaceutical formulations. This paper describes the identification of a key excipient, sodium laurate, which can solubilize LPL in an isotonic environment without heparin or concentrated glycerol. A follow-up multi-variant study was performed to identify the effect of sodium laurate and its interaction with sodium chloride on the solubility and processing conditions of LPL. The LPL concentration (up to 14 mg/mL) achievable in pharmaceutically relevant and salt-free conditions was identified to be closely correlated to the concentration of sodium laurate, which was co-concentrated with LPL. The results that sodium laurate increases stability of LPL characterized by differential scanning calorimetry and UV absorbance spectra suggests that the mechanism of solubilization of LPL by sodium laurate is related to LPL structural stabilization. The findings indicate that substrates and their enzymatic products can be strong stabilizers for other protein molecules.