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Percutaneous Penetration Enhancers Chemical Methods in Penetration Enhancement pp 353–361Cite as

Gene Suppression with Chitosan Nanoparticles

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Abstract

The first tool in gene therapy is DNA internalization for genetic deficiencies, and another tool is used to suppress the biosynthesis of protein by the introduction of antisense oligonucleotides (ASOs) or small interfering ribonucleic acid (siRNAs). ASOs and siRNAs represent an exciting new area for the pharmaceutical industry. These molecules can knock down the expression of target genes through the use of RNA interference (RNAi) pathway.

For the development of ASOs and siRNAs, as therapeutics agents, two key problems must be addressed: serum stability and delivery efficiency/specificity. Further, a suitable delivery system is required. Chitosan nanoparticles are attractive gene delivery systems because they are biodegradable and biocompatible and have low toxicity and immunogenicity. Conventional nanoparticle preparation techniques are used for their production. Chitosan and modified forms of chitosan can be used to prepare nanoparticles. Nanoparticle-based therapeutics can be administered by different routes, such as pulmonary, nasal, dermal, and parenteral.

ASO and siRNA technologies have many similarities, such as gene inhibition and others. However, there are also some differences between these technologies; ASO accumulate in the nucleus of the cell and therefore can be used to alter splicing of mRNA, while siRNAs are known to function in the cytoplasm.

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References

  • Aagard L, Rossi JJ (2007) RNAi therapeutics: principles, prospects and challenges. Adv Drug Deliv Rev 59:75–86

    Article  CAS  Google Scholar 

  • Akbuga J, Kabasakal L, Ozbas-Turan S (2002) Physical and transfectional properties of aged DNA-chitosan microspheres. 10th Annu Meet Eur Soci Gene Ther. Antibes-France

    Google Scholar 

  • Akhtar S (1998) Antisense technology: selection and delivery of optimally acting antisense oligonucleotides. J Drug Target 5:225–234

    Article  PubMed  CAS  Google Scholar 

  • Akhtar S, Hughes MD, Khan A, Bibby M, Hussain M, Nawaz Q et al (2000) The delivery of antisense therapeutics. Adv Drug Deliv Rev 44:3–21

    Article  PubMed  CAS  Google Scholar 

  • Braasch DA, Paroo Z, Constantinescu A, Ren G, Oz OK, Mason RP et al (2004) Biodistribution of phosphodiester and phosphorothioate siRNA. Bioorg Med Chem Lett 14:1139–1143

    Article  PubMed  CAS  Google Scholar 

  • Bumcrot D, Manoharan M, Koteliansky V, Sah DWY (2006) RNAi therapeutics: a potential new class of pharmaceutical drugs. Nat Chem Biol 2:711–719

    Article  PubMed  CAS  Google Scholar 

  • Calvo P, Boughaba AS, Appeal M, Fattal W, Alonso MJ, Couvreur P (1998) Oligonucleotide-chitosan nanoparticles as new gene therapy vector. Proceed Second World Meeting APGI/APV. Paris, p 1111–1112

    Google Scholar 

  • Chen HH, Ho YP, Jiang X, Mao HQ, Wang TH, Leong KW (2008) Quantitative comparison of intracellular unpacking kinetics of polyplexes by a model constructed from quantum dot-free. Mol Ther 16:324–332

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Conner SD, Schmid SL (2003) Regulated portals of entry into the cell. Nature 422:37–44

    Article  PubMed  CAS  Google Scholar 

  • Crooke S (1998) Vitravene-another piece in the mosaic. Antisense Nucleic Acid Drug Dev 8:vii–viii

    Article  PubMed  CAS  Google Scholar 

  • Crooke ST (2004) Progress in antisense technology. Annu Rev Med 55:61–95

    Article  PubMed  CAS  Google Scholar 

  • Dehousse V, Garbacki N, Jaspart S, Castagne D, Piel G, Colige A et al (2010) Comparison of chitosan/siRNA and trimethylchitosan/siRNA complexes behaviour in vitro. Int J Biol Macromol 46:342–349

    Article  PubMed  CAS  Google Scholar 

  • Dokka S, Cooper SR, Kelly S, Hardee GE, Karras JG (2005) Dermal delivery of topically applied oligonucleotides via follicular transport in mouse skin. J Invest Dermatol 124:971–975

    Article  PubMed  CAS  Google Scholar 

  • Duncan R, Richardson SCW (2012) Endocytosis and intracellular trafficking as gateway for nanomedicine delivery: opportunities and challenges. Mol Pharm 9:2380–2402

    Article  PubMed  CAS  Google Scholar 

  • Dung TH, Lee SR, Han SD, Kim SJ, Ju YM, Kim MS et al (2007) Chitosan-TPP nanoparticle as a release system of antisense oligonucleotide in the oral environment. J Nanosci Nanatechnol 7:3695–3699

    Article  CAS  Google Scholar 

  • Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T (2001) Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411:494–498

    Article  PubMed  CAS  Google Scholar 

  • Elmen J, Thonberg H, Ljungberg K, Frieden M, Westergaard M, Xu Y et al (2005) Locked nucleic acid (LNA) mediated improvements in siRNA stability and functionality. Nucleic Acid Res 33:439–447

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391:806–811

    Article  PubMed  CAS  Google Scholar 

  • Gao S, Chen J, Dong L, Ding Z, Yang Y, Zhang J (2005) Targeting delivery of oligonucleotide and plasmid DNA to hepatocyte via galactosylated chitosan vector. Eur J Pharm Biopharm 60:327–334

    Article  PubMed  CAS  Google Scholar 

  • Gao S, Dagnaes-Hansen F, Nielsen EJB, Wengel J, Besenbacher F, Howard KA et al (2009) The effect of chemical modification and nanoparticle formulation on stability and biodistribution of siRNA in mice. Mol Ther 17:1225–1233

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Grosse S, Aron Y, Thevenot G, Francois D, Monsigny M, Fajac I (2005) Potocytosis and cellular exit of complexes as cellular pathways for gene delivery by polycations. J Gene Med 7:1275–1286

    Article  PubMed  CAS  Google Scholar 

  • Guo P, Coban O, Snead NM, Trebley J, Hoeprich S, Guo S et al (2010) Engineering RNA for targeted siRNA delivery and medical application. Adv Drug Deliv Rev 62:650–666

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Guo J, Bourre L, Soden DM, O'sullivan GC, O’Driscoll C (2011) Can non-viral technologies knockdown the barriers to siRNA delivery and achieve the next generation of cancer therapeutics? Biotechnol Adv 29:402–417

    Article  PubMed  CAS  Google Scholar 

  • Hengge UR, Walker PS, Vogel JC (1996) Expression of naked DNA in human, pig, and mouse skin. J Clinic Invest 97:2911–2916

    Article  CAS  Google Scholar 

  • Hong HJ, Jin SE, Park JS, Ahn WS, Kim CK (2008) Accelerated wound healing by smad3 antisense oligonucleotides-impregnated chitosan/alginate polyelectrolyte complex. Biomaterials 29:4831–4837

    Article  PubMed  CAS  Google Scholar 

  • Howard KA (2009) Delivery of RNA interference therapeutics using polycation-based nanoparticles. Adv Drug Deliv Rev 61:710–720

    Article  PubMed  CAS  Google Scholar 

  • Howard KA, Rahbek UL, Liu X, Damgaard CK, Glud SZ, Andersen MO et al (2006) RNA interference in vitro and in vivo using a chitosan/siRNA nanoparticle system. Mol Ther 14:476–484

    Article  PubMed  CAS  Google Scholar 

  • Huang M, Fong CW, Khor E, Lim LY (2005) Transfection efficiency of chitosan vectors: effect of polymer molecular weight and degree of deacetylation. J Control Release 106:391–406

    Article  PubMed  CAS  Google Scholar 

  • Katas H, Alpar HO (2006) Development and characterisation of chitosan nanoparticles for siRNA delivery. J Control Release 115:216–225

    Article  PubMed  CAS  Google Scholar 

  • Kiang T, Bright C, Cheung CY, Stayton PS, Hoffman AS, Leong KW (2004) Formulation of chitosan-DNA nanoparticles with poly(propyl acrylic acid) enhances gene expression. J Biomater Sci Polym Ed 15:1405–1421

    Article  PubMed  CAS  Google Scholar 

  • Lambert G, Fattal E, Couvreur P (2001) Nanoparticulate systems for the delivery of antisense oligonucleotides. Adv Drug Deliv Rev 47:99–112

    Article  PubMed  CAS  Google Scholar 

  • Lebedeva I, Benimetskaya L, Stein CA, Vilenchik M (2000) Cellular delivery of antisense oligonucleotides. Eur J Pharm Biopharm 50:101–119

    Article  PubMed  CAS  Google Scholar 

  • Lee SK, Kumar P (2009) Conditional RNAi: towards a silent gene therapy. Adv Drug Deliv Rev 61:650–664

    Article  PubMed  CAS  Google Scholar 

  • Lee SJ, Son S, Yhee JY, Choi K, Kwon IC, Kim SH et al (2012) Structural modification of siRNA for efficient gene silencing. Biotechnol Adv 31:491–503

    Google Scholar 

  • Leong KW, Mao HQ, Truong-Le VL, Roy K, Walsh SM, August JT (1998) DNA-polycation nanosphere as non-viral gene delivery vehicles. J Control Release 53:183–193

    Article  PubMed  CAS  Google Scholar 

  • Liu X, Howard KA, Dong M, Andersen MO, Rahbek UL, Johnsen MG (2007) The influence of polymeric properties on chitosan/siRNA nanoparticle formulation and gene silencing. Biomaterials 28:1280–1288

    Article  PubMed  CAS  Google Scholar 

  • Mao S, Sun W, Kissel T (2010) Chitosan- based formulations for delivery of DNA and siRNA. Adv Drug Deliv Rev 62:12–27

    Article  PubMed  CAS  Google Scholar 

  • Martimprey H, Vauthier C, Malvy C, Couvreur P (2009) Polymer nanocarriers for the delivery of small fragments of nucleic acids: oligonucleotides and siRNA. Eur J Pharm Biopharm 71:490–504

    Article  PubMed  CAS  Google Scholar 

  • Mehta RC, Stecker KK, Cooper SR, Templin MV, Tsai YJ, Condon TP et al (2000) Intercellular adhesion molecule-1 suppression in skin by topical delivery of anti-sense oligonucleotides. J Invest Dermatol 115:805–812

    Article  PubMed  CAS  Google Scholar 

  • Muthu MS, Feng S (2009) Pharmaceutical stability aspects of nanomedicines. Nanomedicine 4:857–860

    Article  PubMed  CAS  Google Scholar 

  • Nafee N, Taetz S, Schneider M, Schaefer UF, Lehr CM (2007) Chitosan-coated PLGA nanoparticles for DNA/RNA delivery: effect of the formulation parameters on complexation and transfection of antisense oligonucleotides. Nanomedicine 3:173–183

    Article  PubMed  CAS  Google Scholar 

  • Noh SM, Park MO, Shim G, Han SE, Lee HY, Huh JH et al (2010) Pegylated poly-l-arginine derivatives of chitosan for effective delivery of siRNA. J Control Release 145:159–164

    Article  PubMed  CAS  Google Scholar 

  • Ozbas-Turan S, Akbuga J (2011) Plasmid DNA-loaded chitosan/TPP nanoparticles for topical gene delivery. Drug Deliv 18:218–225

    Article  CAS  Google Scholar 

  • Ozbas-Turan S, Akbuga J, Aral C (2002) Controlled release of Interleukin-2 from chitosan microspheres. J Pharm Sci 91:1245–1251

    Article  PubMed  CAS  Google Scholar 

  • Ozbas-Turan S, Akbuga J, Enneli B (2009) Evaluation of antisense oligonucleotide loaded chitosan nanoparticles; characterization and antisense effect. Pharmazie 64:807–811

    PubMed  CAS  Google Scholar 

  • Ozbas-Turan S, Akbuga J, Sezer AD (2010) Topical application of antisense oligonucleotide-loaded chitosan nanoparticles to rats. Oligonucleotides 20:147–153

    Article  PubMed  CAS  Google Scholar 

  • Park S, Lee SK, Lee KY (2011) Oligoarginine-modified chitosan for siRNA delivery. J Control Release 152:e165–e166

    Article  PubMed  CAS  Google Scholar 

  • Park S, Jeong EJ, Lee J, Rhim T, Lee SK, Lee KY (2013) Preparation and characterization of nonaarginine-modified chitosan nanoparticles for siRNA delivery. Carbohydr Polym 92:57–62

    Article  PubMed  CAS  Google Scholar 

  • Rayburn ER, Zhang R (2008) Antisense, RNAi, and gene silencing strategies for therapy: mission possible or impossible. Drug Discov Today 13:513–521

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Regnier V, Doan TL, Preat V (1998) Parameters controlling topical delivery of oligonucleotides by electroporation. J Drug Target 5:275–289

    Article  PubMed  CAS  Google Scholar 

  • Rejman J, Oberle V, Zuhorn IS, Hoekstra D (2004) Size-dependent internalization of particles via the pathways of clathrin- and caveolae- mediated endocytosis. Biochem J 377:159–169

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Romoren K, Aaberge A, Smistad G, Thu B, Evensen O (2004) Long-term stability of chitosan-based polyplexes. Pharm Res 21:2340–2346

    Article  PubMed  CAS  Google Scholar 

  • Sahay G, Alakhova DY, Kabanov AV (2010) Endocytosis of nanomedicine. J Control Release 145:182–195

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Salva E, Kabasakal L, Eren F, Cakalagaoglu F, Ozkan N, Akbuga J (2010) Chitosan/short hairpin RNA complexes for vascular endothelial growth factor suppression invasive breast carcinoma. Oligonucleotides 20:183–190

    Article  PubMed  CAS  Google Scholar 

  • Salva E, Ozkan N, Kabasakal L, Ozbas-Turan S, Akbuga J (2011) The effect of chitosan complexes on biodistribution of siRNA. MUSBED 1:1–7

    CAS  Google Scholar 

  • Schreier H (1994) The new frontier: gene and oligonucleotide therapy. Pharm Acta Helv 68:145–159

    Article  PubMed  CAS  Google Scholar 

  • Soutschek J, Akinc A, Bramlage B, Charisse K, Constien R, Donoghue M et al (2004) Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature 432:173–178

    Article  PubMed  Google Scholar 

  • Tahara K, Sakai T, Yamamoto H, Takeuchi H, Kawashima Y (2008) Establishing chitosan coated PLGA nanosphere platform loaded with wide variety of nucleic acid by complexation with cationic compound for gene delivery. Int J Pharm 354:210–216

    Article  PubMed  CAS  Google Scholar 

  • Tan WB, Jiang S, Zhang Y (2007) Quantum-dot based nanoparticles for targeted silencing of HER2/neu gene via RNA interference. Biomaterials 28:1565–1571

    Article  PubMed  CAS  Google Scholar 

  • Thibault M, Nimesh S, Lavertu M, Buschmann MD (2010) Intracellular trafficking and decondensation kinetics of chitosan–pDNA polyplexes. Mol Ther 18:1787–1795

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Urakami T, Oku N (2007) Current status of siRNA delivery technology and siRNA drug development. Open Drug Deliv J 1:20–27

    Article  CAS  Google Scholar 

  • Wang WX, Gao JQ, Liang WQ (2011) Chitosan-coated liposomes for intracellular oligonucleotides delivery: characteristics and cell uptake behavior. Drug Deliv 18:208–214

    Article  PubMed  CAS  Google Scholar 

  • Weyermann J, Lochmann D, Zimmer A (2004) Comparison of antisense oligonucleotide drug delivery systems. J Control Release 100:411–423

    Article  PubMed  CAS  Google Scholar 

  • Wraight CJ, White PJ (2001) Antisense oligonucleotides in cutaneous therapy. Pharmacol Ther 90:89–104

    Article  PubMed  CAS  Google Scholar 

  • Wraight CJ, White PJ, McKean SC, Fogarty RD, Venables DJ, Liepe IJ et al (2000) Reversal of epidermal hyperproliferation in psoriasis by insulin-like growth factor I receptor antisense oligonucleotides. Nat Biotechnol 18:521–526

    Article  PubMed  CAS  Google Scholar 

  • Zamore PD, Tuschl T, Sharp PA, Bartel DP (2000) RNAi: double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals. Cell 101:25–33

    Article  PubMed  CAS  Google Scholar 

  • Zhou J, Shum KT, Burnett JC, Rossi JJ (2013) Nanoparticle-based delivery of RNAi therapeutics: progress and challenges. Pharmaceuticals 6:85–107

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Authors and Affiliations

  1. Faculty of Pharmacy, Department of Pharmaceutical Biotechnology, Marmara University, Istanbul, Turkey

    Julide Akbuga, Suna Ozbas-Turan & Ceyda Ekentok

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  1. Julide Akbuga
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  2. Suna Ozbas-Turan
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  3. Ceyda Ekentok
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Correspondence to Julide Akbuga .

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Editors and Affiliations

  1. Department of Manufacturing, Apoteka "Beograd", Belgrade, Serbia

    Nina Dragicevic

  2. San Francisco, California, USA

    Howard I. Maibach

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Akbuga, J., Ozbas-Turan, S., Ekentok, C. (2016). Gene Suppression with Chitosan Nanoparticles. In: Dragicevic, N., Maibach, H. (eds) Percutaneous Penetration Enhancers Chemical Methods in Penetration Enhancement. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-47862-2_23

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  • DOI: https://doi.org/10.1007/978-3-662-47862-2_23

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