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Systemic siRNA delivery

The choice between local and systemic delivery depends on what tissues and cell types are targeted. For example, skin and muscle can be better accessed using local siRNA delivery, while lung and tumor can be reached efficiently by both local and systemic siRNA deliveries. There is increasing evidence supporting that siRNA can be efficiently delivered to various tissue types, using different approaches (Fig. 3.2). [Pg.99]

Wang XL, Xu R, Lu ZR (2009) A peptide-targeted delivery system with pH-sensitive amphiphilic cell membrane disruption for efficient receptor-mediated siRNA delivery. J Control Release 134 207-213... [Pg.25]

Fig. 3.2 Challenges of systemic in vivo siRNA delivery. The in vivo application, especially systemic delivery of siRNA, is facing challenges from multiple hurdles in the extracellular environment and various barriers for the intracellular uptake. Addressing those issues is critical for efficient in vivo delivery of siRNA in prechnical animal models for drug target vahdation and potential therapeutics... Fig. 3.2 Challenges of systemic in vivo siRNA delivery. The in vivo application, especially systemic delivery of siRNA, is facing challenges from multiple hurdles in the extracellular environment and various barriers for the intracellular uptake. Addressing those issues is critical for efficient in vivo delivery of siRNA in prechnical animal models for drug target vahdation and potential therapeutics...
The accessibility of different tissue types, the presence of various delivery routes, and a variety of pharmacological requirements makes it impossible to have a universal in vivo delivery system suitable to every scenario of siRNA delivery, hi terms of in vivo delivery vehicles for siRNA, the nonviral carriers are the major type being investigated so far, though some physical and viral delivery approaches are also very effective. The routes of in vivo deliveries are commonly categorized as local or systemic. Some of the delivery vehicles and dehvery routes are very effective in animals for target validation but may not be useful for delivery of siRNA therapeutics in humans (Fig. 3.3). Therefore, in vivo siRNA delivery carriers and methods can also be classified as clinically viable and nonclinically viable, according to their suitability for the human use. [Pg.96]

Fig. 5 Schematic diagram of the siRNA delivery system. A cationic group is universal in all siRNA delivery systems to condense siRNA into nanosized complex. To release the siRNA from the endosome after endocytosis, an endosomal disrupting agent is also essential. PEG modification is also important to improve the pharmacokinetic profile of the complex, as well as to avoid the nonspecific uptake by RES. To achieve the targeted delivery to tumor cells, various ligands including antibody, antibody fragments, peptides, small molecules should be modified to the complex directly or via PEG as a linker... Fig. 5 Schematic diagram of the siRNA delivery system. A cationic group is universal in all siRNA delivery systems to condense siRNA into nanosized complex. To release the siRNA from the endosome after endocytosis, an endosomal disrupting agent is also essential. PEG modification is also important to improve the pharmacokinetic profile of the complex, as well as to avoid the nonspecific uptake by RES. To achieve the targeted delivery to tumor cells, various ligands including antibody, antibody fragments, peptides, small molecules should be modified to the complex directly or via PEG as a linker...
To develop an efficient siRNA cancer therapy, targeted delivery of siRNA to tumor cells is the primary requisite to overcome nonspecific side effects, as well as increase the therapeutic effect. Most cancer cells express unique or overexpressed receptors/antigens on their cell surface which can bind various ligands including antibodies, antibody fragments, small molecules, peptides, and aptamers. A number of tumor-specific ligands have been modified to the siRNA delivery system to enhance the specific cellular uptake in tumor cells. The most commonly used ligands are described below. [Pg.426]

Peer D, Park EJ, Morishita Y, Carman CV, Shimaoka M. Systemic leukocyte-directed siRNA delivery revealing cyclin D1 as an anti-inflammatory target. Science 2008 319 627-630. [Pg.512]

In an another study, they reported a PIC micelle siRNA delivery system prepared from the block copolymer poly(ethylene glycol)-Wock-poly(L-lysine) (PEG-ft-PLL) modified with the cross-linking reagent 2-iminothiolane (2-IT, Traut s reagent) (Figure 54.4). ... [Pg.1274]

Tamura, A. Nagasaki, Y. Smart siRNA delivery systems based on polymeric nanoassembUes and nanoparticles. Nanomedicine 2010, 5 (7), 1089—1102. [Pg.1300]

Swami, A., Kurupati, R.K., Pathak, A., Singh, Y., Kumar, P., Gupta, K.C., 2007. A unique and highly efficient non-viral DNA/siRNA delivery system based on PEIbisepoxide nanoparticles. Biochem. Biophys. Res. Commun. 362 (4), 835—841. [Pg.176]

In order to overcome the limitations associated with siRNA delivery in vivo, a group of dendritic nanocarriers derived either fromPG or PEI were synthesized and their silencing efficiency was evaluated. Among the nanocarriers evaluated in this study, the best siRNA transfection efficiency with regard to toxicity was observed for PG amine. In general, successful systemic delivery... [Pg.263]


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