title: A frustrating problem: accelerated blood clearance of PEGylated solid lipid nanoparticles following subcutaneous injection in rats.
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 regional lymph nodes also play a promotive role in this phenomenon, although the exact lymphocytes causing this phenomenon remain unclear. Our observations may thus have important implications for considering combination therapy with PEGylated productions requiring different administration routes such as intravenous and subcutaneous injection, and great care is needed.
authors.affiliation: College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, PR China.
authors.forename: Yongxue
authors.initials: Y
authors.lastname: Zhao
authors.forename: Chunling
authors.initials: C
authors.lastname: Wang
authors.forename: Long
authors.initials: L
authors.lastname: Wang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Yang
authors.forename: Wenya
authors.initials: W
authors.lastname: Tang
authors.forename: Zhennan
authors.initials: Z
authors.lastname: She
authors.forename: Yihui
authors.initials: Y
authors.lastname: Deng
mesh_terms: D000818:Animals; D003102:Colloids; D007075:Immunoglobulin M / Q000276:immunology; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008055:Lipids / Q000737:chemistry* / Q000493:pharmacokinetics; D008198:Lymph Nodes / Q000378:metabolism*; D008297:Male; D053758:Nanoparticles; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D003102:Colloids; D007075:Immunoglobulin M; D008055:Lipids; D011092:Polyethylene Glycols