Liposome-targeted recombinant human acid sphingomyelinase: Production, formulation, and in vitro evaluation

European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V
Mohammed H AldosariEnrico Mastrobattista

Abstract

Niemann-Pick disease type B is a hereditary rare condition caused by deficiency of the acid sphingomyelinase (ASM) that is needed for lysosomal hydrolysis of sphingomyelin to ceramide and phosphocholine. This deficiency leads to a massive accumulation of sphingomyelin in cells throughout the body, predominantly in the liver, spleen and lungs. Currently, there is no effective treatment available. Olipudase alfa (recombinant human acid sphingomyelinase; rhASM) is an investigational drug that has shown promising results. However, dose-dependent toxicity was observed in mice upon the intravenous administration of rhASM, potentially due to the systemic release of ceramide upon the extracellular degradation of sphingomyelin by rhASM. Using a nanocarrier to deliver the rhASM to cells could improve the therapeutic window by shielding the rhASM to prevent the off-target degradation of sphingomyelin. For this aim, we recombinantly expressed hASM in human cells and loaded it into different liposomal formulations at a drug-to-lipid ratio of 4% (w/w). Among four formulations, the liposomal rhASM formulation with the composition DPPC:DOPS:BMP:CHOL:DiD (59:20:10:10:1 mol%) was selected because of its superiority concerning the encapsulation e...Continue Reading

Citations

Jul 1, 2020·Expert Opinion on Biological Therapy·Saptashwa DattaHatem Zayed
Jun 27, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Enrico Mastrobattista
Aug 28, 2021·International Journal of Molecular Sciences·Bernadette Breiden, Konrad Sandhoff

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