A frustrating problem: accelerated blood clearance of PEGylated solid lipid nanoparticles following subcutaneous injection in rats

European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V
Yongxue ZhaoYihui Deng

Abstract

Colloidal particles have preferential access to the lymphatic system following subcutaneous administration, achieving lymphatic targeting by drug accumulation in the regional lymph nodes. Moreover, the surface PEGylated colloidal particles have shown enhanced drainage into lymphatics and uptake by macrophages of the regional lymph nodes after subcutaneous injection. Nevertheless, it is reported that upon repeated intravenous injection, the PEG-specific IgM produced by the administration of the PEGylated colloidal particles markedly accelerates the clearance of subsequent doses of PEGylated particles. In this article, we report that the first subcutaneous injection of PEGylated solid lipid nanoparticles also induces the intravenously administered PEGylated particles to be cleared very rapidly from the circulation, and the "ABC index," a parameter for the intensity of accelerated blood clearance, for subcutaneous injection was equivalent to or even lower than that following the first intravenous injection. Moreover, the small quantities of distributed particles in the spleen after the first s.c. dose but the significantly higher elimination rate of the second i.v. dose, strongly suggest that, in addition to the spleen, the region...Continue Reading

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