Antisense nanoparticles

Nanosized objects perform various functions in the biomedical field. In the human body, nanosized particulate substances behave very differently from larger particles. In 1986, Maeda et al. found that the stained albumin, having a size of several nanometers, naturally accumulates in the region of cancerous tissues, which is now well known as the enhanced permeability and retention (EPR) effect. Many studies in the field of nanoparticles are based on this finding. Another application of nanoparticles is the delivery system using various polyplexes that are composed of carrier molecules and plasmid DNA or nucleic acid drugs such as antisenses and siRNA. In addition, nanofibers are mainly used for biodegradable scaffolds in tissue... 

I. Aynie, C. Vauthier, E. Fattal, and M. Foulquier, Alginate nanoparticles as a noval carrier for antisense oligonucleotides, in Future Strategies for Drug Delivery with Particulate Systems, Stuttgart, 1997, pp. 11-16. 

Microspheres and nanoparticles often consist of biocompatible polymers and belong either to the soluble or the particle type carriers. Besides the aforementioned HPMA polymeric backbone, carriers have also been prepared using dextrans, ficoll, sepharose or poly-L-lysine as the main carrier body. More recently alginate nanoparticles have been described for the targeting of antisense oligonucleotides [28]. As with other polymeric carrier systems, the backbone can be modified with e.g. sugar molecules or antibody fragments to introduce cellular specificity. 

Zimmer, A. (1999). Antisense oligonucleotide delivery with polyhexylcyanoacrylate nanoparticles as carriers. Methods, 18(3), 286-295, 322. 

Systemic Delivery and Pre-clinical Evaluation of Nanoparticles Containing Antisense Oligonucleotides and siRNAs... 

We and others have demonstrated that Raf-1 protein serine/threonine kinase is a druggable signaling molecule in cancer therapy (1,13,17,21-25). Our laboratory has developed a novel cationic liposomal formulation for systemic delivery of intact raf ASO (LErafAON) to normal and tumor tissues in mice (13,17). The liposome-entrapped raf antisense oligonucleotide (LErafAON) is also the first liposomal ASO drug tested in humans (26,27). Systemically delivered cationic liposomal nanoparticles containing rafsiRNA (LErafsiRNA) also inhibit Raf-1 protein expression in tumor and most normal tissues in human prostate tumor (PC-3)-bearing athymic mice (Fig. 1 and Color Plate 1, see Color Plate Section). 

Aynie IC, Vauthier C, Fattal E, Foulquier M, Couvreur P (1998) Alginate nanoparticles as a novel carrier for antisense oligonucleotide. In Diederichs JE, Muler R (eds), Future Strategies of Drug Delivery with Particulate Systems. Stuttgart Medipharm Scientific Publisher, pp 5-10... 

Poly(alkyl-cyanoacrylate) Nanoparticles The applications of poly(alkyl-cyanoacrylate) nanoparticles have been reviewed elsewhere and therefore only representative examples are described [102], Because of their adhesive properties, nanoparticles have the potential to prophylactically treat candidiasis of the oral cavity [121], Not surprisingly, poly(alkyl-cyanoacrylate) nanoparticles have been used to deliver drugs to tumors [122], Enhanced absorption and prolonged hypoglycemic effect were observed when insulin was delivered in poly(alkyl-cyanoacrylate) nanoparticles [121], Nuclear accumulation of antisense oligonucleotides into vascular smooth muscle cells was increased when delivered using poly(alkyl-cyanoacrylate) nanoparticles [123]. Dextran-coated poly(alkyl-... 

Lochmann, D., et al. (2005), Albumin-protamine-oligonucleotide nanoparticles as a new antisense delivery system. Part 1 Physicochemical characterization, Eur. J. Pharm. Biopharm., 59(3), 419—429. 

Chavany, C. Ledoan, T. Couvreur, P. Puisieux, F. Helene, C. Polyalkylcyanoacrylate nanoparticles as polymeric carriers for antisense oligonucleotides. Pharm. Res. 1992, 9, 441 49. 

Since the first reports on magnetically enhanced nucleic acid delivery in the year 2000 (1,2), magnetofection has become a well-established method and has been predominantly used for in vitro applications. It has been shown to potentiate viral (3, 4) and non-viral nucleic acid delivery, including plasmids or small constructs such as antisense oligonucleotides, and synthetic siRNA and PCR products (5-10). The nucleic acids can be directly associated with magnetic nanoparticles in... 

Cytoplasm is an important target for si RNA and antisense oligonucleotides whereas transcription factors and plasmid DNA should be delivered into the nucleus (Figure 22.2). Cytoplasm is a highly viscous medium where passive diffusion of nanoparticles, and macromolecules are very slow [27]. It is very appealing to search for the means by which the nanoparticulate transport in the cytoplasm and delivery into the nucleus can be maximized [28]. Specific nuclear localizing peptides have been attached to the nanoparticulates for the nuclear delivery but their efficacy is still not adequate [29]. 

Antide stmcture 1408 Antiepileptic dmgs 58 Antigen-nanoparticle conjugate 1310 Antigen-presenting cell 191, 360 Antihemolytic factor Vlll, see fVlll Antihemophilia agents 454 Antinuclear autoantibodies, mononuclear 1371 Antiperinuclear factor 1192 Antisense RNA... 

Zobel, H-P, Atmaca, A, Werner, D, Noe, C R, Stieneker, F, Kreuter, J, Zimmer, A, Preparation of Antisense Nucleic Acid loaded Nanoparticles and Liposomes. Proceed. 2nd Antisense Nucleic Acids, Garmisch-Partenkirchen, 1995 p. 77. 

Zimmer A (1999). Antisense Oligonucleotide Delivery with Polyhexylcyanoacrylate Nanoparticles as Carriers. Methods. 18 286-295. 

Zobel H P, Kreuter J, Werner D, et al. (1997). Cationic polyhexylcyanoacrylate nanoparticles as carriers for antisense oligonucleotides. Antisense Nucleic Acid Drug Dev. 7 483-493. 

Therapeutics DNA-Modified Gold Nanoparticles as Antisense Agents, 429... 

THERAPEUTICS DNA-MODIFIED GOLD NANOPARTICLES AS ANTISENSE AGENTS... 

Kakizawa Y, Kataoka K. Block copolymer self-assembly into monodispersive nanoparticles with hybrid core of antisense DNA and calcium phosphate. Langmuir 2002 18 4539-4543. 

Gotting, N., Fritz, H., Maier, M., von Stamm, J., Schools, T. and Bayer, E., Effects of oligonucleotide adsorption on the physicochemical characteristics of a nanoparticle-based model delivery for antisense drugs. Colloid Polym. Sci., Til, 145, 1999. 

Azizi, E., Namazi, A., Haririan, 1., Fouladdel, S., Khoshayand, M. R., Shotorbani, Parisa, Y., Nomani, A., and Gazori,T. (2010). Release profile and stability evaluation of optimized chitosan/alginate nanoparticles as EGFR antisense vector, Int J. Nanomed., 5,455-461. 

Ozbas-Turan, S., Akbuga, J., Sezer, A. D. (2010). Topical application of antisense oligonucleotide-loaded chitosan nanoparticles to rats. Oligonucleotides. 20,147-53. 

Gazori, T., BChoshayand, M.R., Azizi, E., Yazdizade, P., Normani, A., Haririan, I. Evaluation of alginate/chitosan nanoparticles as antisense delivery vecton Formulation, optimization and in vitro characterization. Carbohydr. Polym. 77, 599-606 (2009)... 

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