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In Vitro PDGF-B Gene Silencing Studies and In Vivo Delivery of siRNA to the Rat Kidney Using Chitosan/siRNA Nanoplexes

Year 2016, Volume: 20 Issue: 3, 263 - 268, 04.04.2016

Emine Şalva Suna Özbaş Turan Saadet Alan Jülide Akbuğa

Abstract

The targeting of specific genes responsible from onset and progression of kidney diseases offer a new therapeutic strategy in the field of renal gene therapy. The altered expression of platelet derived growth factor (PDGF) is an important marker of renal diseases. In this study, we investigated in vitro gene silencing efficiency of chitosan nanoplexes containing PDGF-B and PDGFR-β targeted siRNAs in the kidney cell lines including HEK-293 and MDCK and delivery to the kidney as an in vivo delivery system. As a result, PDGF-B expression was significantly inhibited by co-delivery of chitosan/siPDGF-B and siPDGFR-β nanoplexes prepared using in the different weight ratios (10/1, 20/1 and 50/1). When 20/1 and 50/1 weight ratios of chitosan nanoplexes were i.v. injected to rats, chitosan/FITC-siPDGFB nanoplexes were reached to kidney tissue at 4 h after intravenous injection. These results suggest that delivery of siRNA using chitosan nanoplexes may be effective for the therapy of kidney diseases. 

Keywords

siRNA PDGF-B PDGFR-β chitosan nanoplexes kidney

References

  • Levey AS, Atkins R, Coresh J, Cohen EP, Collins AJ, Eckardt K-U, Nahas ME, Jaber BL, Jadoul M, Levin A, Powe NR, Rossert J, Wheeler DC, Lameire N, Eknoyan G. Chronic kidney disease as a global public health problem: Approaches and initiatives – a position statement from kidney disease improving global outcomes. Kidney Int 2007;72(3):247-259.
  • Stokman G, Qin Y, Rácz Z, Hamar P, Price LS. Application of siRNA in targeting protein expression in kidney disease. Adv Drug Del Rev 2010;62:1378-1389.
  • Luo GH, Lu YP, Song J, Yang L, Shi YJ, Li YP. Inhibition of connective tissue growth factor by small interfering RNA prevents renal fibrosis in rats undergoing chronic allograft nephropathy. Transplant Proc 2008;40: 2365-2369.
  • Aliabadi HM, Landry B, Sun C, Tang T, Uludağ H. Supramolecular assemblies in functional siRNA delivery: Where do we stand? Biomaterials 2012;33: 2546-2569.
  • Akhtar S, Benter IF. Nonviral delivery of synthetic siRNAs in vivo J Clin Invest 2007;117: 3623-3632.
  • Scindia YM, Deshmukh US, Bagavant H. Mesangial pathology in glomerular disease: targets for therapeutic intervention. Adv Drug Del Rev 2010; 62: 1337-1343.
  • Rudzinski WE, Aminabhavi TM. Chitosan as a carrier for targeted delivery of small interfering RNA. Int J Pharm 2010; 399:1-11.
  • Salva E, Kabasakal L, Eren F, Ozkan N, Cakalagaoglu F, Akbuga J. Local delivery of chitosan/VEGF siRNA nanoplexes reduces angiogenesis and growth of breast cancer in vivo. Nucleic Acid Ther 2012; 22:40-48.
  • Erdem-Cakmak F, Ozbas-Turan S, Salva E, Akbuga J. Comparision of VEGF gene silencing efficiencies of chitosan and protamine complexes containing shRNA. Cell Biol Int 2014; 38:1260-1270.
  • Choi CHJ, Zuckerman JE, Webster P, Davis ME. Targeting kidney mesangium by nanoparticles of defined size. PNAS 2011; 108(16): 6656-6661.
  • Zuckerman JE, Gale A, Wu P, Ma R, Davis ME. siRNA delivery to the glomerular mesangium using polycationic cyclodextrin nanoparticles containing siRNA. Nuc Acid Ther 2012; 25(2): 53-64.
  • Gao S, Hein S, Dagnæs-Hansen F, Weyer K, Yang C, Nielsen R, Christensen EI, Fenton RA, Kjems J. Megalin-mediated specific uptake of chitosan/siRNA nanoparticles in mouse kidney proximal tubule epithelial cells enables AQP1 gene silencing. Theranostics 2014; 4(10):1039-1051.
  • Floege J, Eitner F, Alpers CE. A new look at Platelet-Derived Growth Factor in renal disease. JAm Soc Nephrol 2008;19:12-23.
  • Salva E, Akbuga J. In vitro silencing effect of chitosan nanoplexes containing siRNA expressing vector targeting VEGF in breast cancer cell lines. Pharmazie 2010;65:896-902.
  • Eto S, Isome M, Sano H, Fukuda Y, Kawasaki Y, Suzuki J, Igarashi K, Satriano J, Suzuki H. Agmantine suppresses mesangial cell proliferation by modulating polyamine metabolism. Tohoku J Exp Med 2006; 210:145-151.
  • Xu CF, Wang J. Delivery systems for siRNA drug development in cancer therapy. Asian J Pharm Sci. 2015;10:1-12.
  • Deng Y, Wang CC, Choy KW, Du Q, Chen J, Wong Q et al. Therapeutic potentials of gene silencing by RNA interference: Principles, challenges and new strategies. Gene. 2014; 538:217-227.
  • David S, Pitard B, Benoît JP, Passirani C. Non-viral nanosystems for systemic siRNA delivery. Pharmacol Res 2010;62:100-114.
  • Reischl D, Zimmer A. Drug delivery of siRNA therapeutics: potentials and limits of nanosystems. Nanomedicine: Nanotechnol, Biol Med 2009;5:8-20.
  • Shimizu H, Hori Y, Kaname S, Yamada K, Nishiyama N, Matsumoto S, Miyata K, Oba M, Yamada A, Kataoka K, Fujita T. siRNA-based therapy ameliorates glomerulonephritis. J Am Soc Nephrol 2010;21:622-633.
  • Gao S, Dagnaes-Hansen F, Nielsen EJB, Wengel J, Besenbacher F, Howard KA, Kjems J. The effect of chemical modification and nanoparticle formulation on stability and biodistribution of siRNA in mice. Mol Ther 2009;17:1225-1233.
  • Şalva E, Ozkan N, Kabasakal L, Turan SO, Akbuğa J. The Effect of chitosan complexes on biodistribution of siRNA. J Marmara Univ Inst of Health Sci (MUSBED) 2011;1(1):1-7.

Year 2016, Volume: 20 Issue: 3, 263 - 268, 04.04.2016

Emine Şalva Suna Özbaş Turan Saadet Alan Jülide Akbuğa

Abstract

References

  • Levey AS, Atkins R, Coresh J, Cohen EP, Collins AJ, Eckardt K-U, Nahas ME, Jaber BL, Jadoul M, Levin A, Powe NR, Rossert J, Wheeler DC, Lameire N, Eknoyan G. Chronic kidney disease as a global public health problem: Approaches and initiatives – a position statement from kidney disease improving global outcomes. Kidney Int 2007;72(3):247-259.
  • Stokman G, Qin Y, Rácz Z, Hamar P, Price LS. Application of siRNA in targeting protein expression in kidney disease. Adv Drug Del Rev 2010;62:1378-1389.
  • Luo GH, Lu YP, Song J, Yang L, Shi YJ, Li YP. Inhibition of connective tissue growth factor by small interfering RNA prevents renal fibrosis in rats undergoing chronic allograft nephropathy. Transplant Proc 2008;40: 2365-2369.
  • Aliabadi HM, Landry B, Sun C, Tang T, Uludağ H. Supramolecular assemblies in functional siRNA delivery: Where do we stand? Biomaterials 2012;33: 2546-2569.
  • Akhtar S, Benter IF. Nonviral delivery of synthetic siRNAs in vivo J Clin Invest 2007;117: 3623-3632.
  • Scindia YM, Deshmukh US, Bagavant H. Mesangial pathology in glomerular disease: targets for therapeutic intervention. Adv Drug Del Rev 2010; 62: 1337-1343.
  • Rudzinski WE, Aminabhavi TM. Chitosan as a carrier for targeted delivery of small interfering RNA. Int J Pharm 2010; 399:1-11.
  • Salva E, Kabasakal L, Eren F, Ozkan N, Cakalagaoglu F, Akbuga J. Local delivery of chitosan/VEGF siRNA nanoplexes reduces angiogenesis and growth of breast cancer in vivo. Nucleic Acid Ther 2012; 22:40-48.
  • Erdem-Cakmak F, Ozbas-Turan S, Salva E, Akbuga J. Comparision of VEGF gene silencing efficiencies of chitosan and protamine complexes containing shRNA. Cell Biol Int 2014; 38:1260-1270.
  • Choi CHJ, Zuckerman JE, Webster P, Davis ME. Targeting kidney mesangium by nanoparticles of defined size. PNAS 2011; 108(16): 6656-6661.
  • Zuckerman JE, Gale A, Wu P, Ma R, Davis ME. siRNA delivery to the glomerular mesangium using polycationic cyclodextrin nanoparticles containing siRNA. Nuc Acid Ther 2012; 25(2): 53-64.
  • Gao S, Hein S, Dagnæs-Hansen F, Weyer K, Yang C, Nielsen R, Christensen EI, Fenton RA, Kjems J. Megalin-mediated specific uptake of chitosan/siRNA nanoparticles in mouse kidney proximal tubule epithelial cells enables AQP1 gene silencing. Theranostics 2014; 4(10):1039-1051.
  • Floege J, Eitner F, Alpers CE. A new look at Platelet-Derived Growth Factor in renal disease. JAm Soc Nephrol 2008;19:12-23.
  • Salva E, Akbuga J. In vitro silencing effect of chitosan nanoplexes containing siRNA expressing vector targeting VEGF in breast cancer cell lines. Pharmazie 2010;65:896-902.
  • Eto S, Isome M, Sano H, Fukuda Y, Kawasaki Y, Suzuki J, Igarashi K, Satriano J, Suzuki H. Agmantine suppresses mesangial cell proliferation by modulating polyamine metabolism. Tohoku J Exp Med 2006; 210:145-151.
  • Xu CF, Wang J. Delivery systems for siRNA drug development in cancer therapy. Asian J Pharm Sci. 2015;10:1-12.
  • Deng Y, Wang CC, Choy KW, Du Q, Chen J, Wong Q et al. Therapeutic potentials of gene silencing by RNA interference: Principles, challenges and new strategies. Gene. 2014; 538:217-227.
  • David S, Pitard B, Benoît JP, Passirani C. Non-viral nanosystems for systemic siRNA delivery. Pharmacol Res 2010;62:100-114.
  • Reischl D, Zimmer A. Drug delivery of siRNA therapeutics: potentials and limits of nanosystems. Nanomedicine: Nanotechnol, Biol Med 2009;5:8-20.
  • Shimizu H, Hori Y, Kaname S, Yamada K, Nishiyama N, Matsumoto S, Miyata K, Oba M, Yamada A, Kataoka K, Fujita T. siRNA-based therapy ameliorates glomerulonephritis. J Am Soc Nephrol 2010;21:622-633.
  • Gao S, Dagnaes-Hansen F, Nielsen EJB, Wengel J, Besenbacher F, Howard KA, Kjems J. The effect of chemical modification and nanoparticle formulation on stability and biodistribution of siRNA in mice. Mol Ther 2009;17:1225-1233.
  • Şalva E, Ozkan N, Kabasakal L, Turan SO, Akbuğa J. The Effect of chitosan complexes on biodistribution of siRNA. J Marmara Univ Inst of Health Sci (MUSBED) 2011;1(1):1-7.
There are 22 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Articles
Authors

Emine Şalva

Suna Özbaş Turan This is me

Saadet Alan This is me

Jülide Akbuğa This is me

Publication Date April 4, 2016
Published in Issue Year 2016 Volume: 20 Issue: 3

Cite

APA Şalva, E., Turan, S. Ö., Alan, S., Akbuğa, J. (2016). In Vitro PDGF-B Gene Silencing Studies and In Vivo Delivery of siRNA to the Rat Kidney Using Chitosan/siRNA Nanoplexes. Marmara Pharmaceutical Journal, 20(3), 263-268. https://doi.org/10.12991/mpj.82721
AMA Şalva E, Turan SÖ, Alan S, Akbuğa J. In Vitro PDGF-B Gene Silencing Studies and In Vivo Delivery of siRNA to the Rat Kidney Using Chitosan/siRNA Nanoplexes. Marmara Pharm J. May 2016;20(3):263-268. doi:10.12991/mpj.82721
Chicago Şalva, Emine, Suna Özbaş Turan, Saadet Alan, and Jülide Akbuğa. “In Vitro PDGF-B Gene Silencing Studies and In Vivo Delivery of SiRNA to the Rat Kidney Using Chitosan/SiRNA Nanoplexes”. Marmara Pharmaceutical Journal 20, no. 3 (May 2016): 263-68. https://doi.org/10.12991/mpj.82721.
EndNote Şalva E, Turan SÖ, Alan S, Akbuğa J (May 1, 2016) In Vitro PDGF-B Gene Silencing Studies and In Vivo Delivery of siRNA to the Rat Kidney Using Chitosan/siRNA Nanoplexes. Marmara Pharmaceutical Journal 20 3 263–268.
IEEE E. Şalva, S. Ö. Turan, S. Alan, and J. Akbuğa, “In Vitro PDGF-B Gene Silencing Studies and In Vivo Delivery of siRNA to the Rat Kidney Using Chitosan/siRNA Nanoplexes”, Marmara Pharm J, vol. 20, no. 3, pp. 263–268, 2016, doi: 10.12991/mpj.82721.
ISNAD Şalva, Emine et al. “In Vitro PDGF-B Gene Silencing Studies and In Vivo Delivery of SiRNA to the Rat Kidney Using Chitosan/SiRNA Nanoplexes”. Marmara Pharmaceutical Journal 20/3 (May 2016), 263-268. https://doi.org/10.12991/mpj.82721.
JAMA Şalva E, Turan SÖ, Alan S, Akbuğa J. In Vitro PDGF-B Gene Silencing Studies and In Vivo Delivery of siRNA to the Rat Kidney Using Chitosan/siRNA Nanoplexes. Marmara Pharm J. 2016;20:263–268.
MLA Şalva, Emine et al. “In Vitro PDGF-B Gene Silencing Studies and In Vivo Delivery of SiRNA to the Rat Kidney Using Chitosan/SiRNA Nanoplexes”. Marmara Pharmaceutical Journal, vol. 20, no. 3, 2016, pp. 263-8, doi:10.12991/mpj.82721.
Vancouver Şalva E, Turan SÖ, Alan S, Akbuğa J. In Vitro PDGF-B Gene Silencing Studies and In Vivo Delivery of siRNA to the Rat Kidney Using Chitosan/siRNA Nanoplexes. Marmara Pharm J. 2016;20(3):263-8.