Question

A major route of elimination of siRNA from the bloodstream is through kidney filtration. As naked siRNA can pass through the glomerular filtration barrier99, many delivery systems prevent renal clearance by encapsulating siRNA into particles larger than ~20nm17. It should be noted that several highly efficacious delivery systems, including Dynamic PolyConjugates (DPCs)100 and triantennary N-acetylgalactosamine (GalNAc) conjugates101, are smaller than this cutoff, which probably reflects the fact that these delivery systems mainly deliver their payloads in the first pass through the liver. Some nanoparticulate systems undergo disassembly in the glomerulus102,103. Interaction with the negatively charged glomerular basement membrane can disrupt the electrostatic interactions that are essential to the stability of certain particles, which causes disassembly and passage of siRNA into urine102,10

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Answer 1

From the bloodstream, siRNA will undergo initial distribution through a circulatory system in a few minutes. siRNA undergoes certain pathways to get eliminated from blood. It will get accumulated in the liver and through renal filtration and finally it will be excluded through urine. Many delivery systems blocks the passage of siRNA through kidneys by enfolding in to larger particles of size 20 nm17. Glomerular basement membrane (GBM) is the main component of renal filtration barrier. GBM causes disassembly of catatonic cyclodextrin containing polymer based siRNA nanoparticles, thereby facilitating rapid elimination of siRNA from circulation. siRNA generally assembled by electrostatic interactions between catatonic delivery components but that will be disturbed by GBM ( when siRNA binds with negativity charged GBM) since siRNA normally accumulate in GBM.