کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2083943 1545359 2012 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A frustrating problem: Accelerated blood clearance of PEGylated solid lipid nanoparticles following subcutaneous injection in rats
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیوتکنولوژی یا زیست‌فناوری
پیش نمایش صفحه اول مقاله
A frustrating problem: Accelerated blood clearance of PEGylated solid lipid nanoparticles following subcutaneous injection in rats
چکیده انگلیسی

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.

Subcutaneous injection of PEGylated solid lipid nanoparticles induced the very rapid clearance of intravenously administered PEGylated particles from the circulation, and the regional lymph nodes might play a promotive role in this phenomenon.Figure optionsDownload high-quality image (135 K)Download as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmaceutics and Biopharmaceutics - Volume 81, Issue 3, August 2012, Pages 506–513
نویسندگان
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