Open Access Open Access  Restricted Access Subscription Access
Open Access Open Access Open Access  Restricted Access Restricted Access Subscription Access

Silk Fibroin:A Boon to Pharmaceutical and Biomedical Applications


Affiliations
1 Department of Pharmaceutics, STES’s Sinhgad College of Pharmacy, Vadgaon (Bk.), Pune - 411041 (M.S.), India
     

   Subscribe/Renew Journal


Silks are naturally occurring polymers that have been used clinically as sutures for centuries. When naturally extruded from insects or worms, silk is composed of a filament core protein, termed fibroin. To date fibroin from Bombyxmori silk worm has been the dominant source for silk-based biomaterials studied. Silk fibroin (SF) is a naturally occurring protein polymer with several unique properties that make it a suitable material for incorporation into a variety of drug delivery vehicles capable of delivering a range of therapeutic agents. SF is biocompatible, slowly biodegradable, and endowed with excellent mechanical properties and process ability. So far, the main focus of SF drug delivery systems has been on tissue regeneration applications. For instance, growth factor loaded SF scaffolds were suggested for the tissue engineering of bone and cartilage, as well as for vascular and nerve regeneration devices and wound healing products. Moreover, SF matrices were proposed for oral, transmucosal and ocular drug delivery. SF matrices have been shown to successfully deliver anticancer drugs, small molecules, and biomolecules. This article will provide an in-depth discussion on the SF properties and pharmaceutical and drug delivery applications of Silk fibroin in nanoparticles.

Keywords

Silk, Silk Fibroin, Bombyxmori, Pharmaceuticals, Drug Delivery.
Subscription Login to verify subscription
User
Notifications
Font Size


  • Valluzzi R, Winkler S, Wilson D, Kaplan DL. Silk: molecular organization and control of assembly. Philosophical Transactions of the Royal Society of London B: Biological Science.2002; 357 (1418): 165-167.
  • Chen X, Knight DP, Shao Z, Vollrath F. Conformation transition in silk protein films monitored by time-resolved Fourier transform infrared spectroscopy: Effect of potassium ions on Nephilaspidroin films. Biochemistry. 2002; 41 (50): 14944-14950.
  • Van Beek JD, Hess S, Vollrath F, Meier BH. The molecular structure of spider dragline silk: folding and orientation of the protein backbone. Proceedings of the National Academy of Sciences. 2002; 99 (16): 10266-10271.
  • Vollrath F, Madsen B, Shao Z. The effect of spinning conditions on the mechanics of a spider's dragline silk, Proceedings of the Royal Society of London B: Biological Sciences.2001; 268 (1483): 2339-2346.
  • Wilson D, Valluzzi R, Kaplan D. Conformational transitions in model silk peptides. Biophysical Journal. 2000; 78 (5): 2690-2701.
  • Knight DP, Vollrath F. Biological liquid crystal elastomers. Philosophical Transactions of the Royal Society of London B: Biological Science. 2002; 357 (1418): 155-163.
  • Vollrath F, Knight DP. Liquid crystalline spinning of spider silk. Nature.2001; 410 (6828): 541-548.
  • Upadhyay VB, Tiwari S. Changes in protein profile in haemolymph of Bombyxmori larvae in response to Aloe vera essential oil. Research Journal of Science and Technology. 2015; 7 (1): 29-34.
  • Altman GH, Diaz F, Jakuba C, Calabro T, Horan RL, Chen J, Lu H, Richmond J, Kaplan DL. Silk-based biomaterials. Biomaterials.2003; 24 (3): 401-416.
  • Nair LS, Laurencin CT. Polymers as biomaterials for tissue engineering and controlled drug delivery. Advances in Biochemical Engineering/Biotechnology Journal.2006; 102: 4790.
  • Malafaya PB, Silva GA, Reis RL. Natural-origin polymers as carriers and scaffolds for biomolecules and cell delivery in tissue engineering applications. Advanced Drug Delivery Reviews.2007; 59 (4); 207-233.
  • Mano JF, Silva GA, Azevedo HS, Malafaya PB, Sousa RA, Silva SS, Boesel LF, Oliveira JM, Santos TC, Marques AP, Neves NM, Reis RL. Natural origin biodegradable systems in tissue engineering and regenerative medicine: present status and some moving trends. Journal of the Royal Society Interface.2007; 4 (17): 999-1030.
  • Kaplan DL, Adams WW, Farmer B and Viney C. Editors. Silk Polymers: Materials Science and Biotechnology. ACS Symposium Series. 1994; Vol. 544, 1994: pp. 2-16.
  • Wang Y, Kim HJ, Vunjak-Novakovic G, Kaplan DL. Stem cellbased tissue engineering with silk biomaterials. Biomaterials. 2006; 27: 6064-6082.
  • Makaya K, Terada S, Ohgo K, Asakura T. Comparative study of silk fibroin porous scaffolds derived from salt/water and sucrose/hexafluoroisopropanol in cartilage formation. Journal of Bioscience and Bioengineering. 2009; 108: 68-75.
  • Lazaris A, Arcidiacono S. Spider silk fibers spun from soluble recombinant silk produced in mammalian cells. Science. 2002; 295: 472-476
  • Guerette PA, Ginzinger DG, Weber BH, Gosline JM. Silk properties determined by gland-specific expression of a spider fibroin gene family. Science. 1996; 272:112-115.
  • Hinman MB, Lewis RV. Isolation of a clone encoding a second dragline silk fibroin. Nephilaclavipes dragline silk is a two protein fiber. The Journal of Biological Chemistry. 1992; 267: 1932019324.
  • Winkler S, Wilson D, Kaplan DL. Controlling beta-sheet assembly in genetically engineered silk by enzymatic phosphorylation/ dephosphorylation. Biochemistry. 2000; 39: 12739-12746
  • Simmons AH, Michal CA, Jelinski LW. Molecular orientation and two-component nature of the crystalline fraction of spider dragline silk. Science. 1996; 271: 84-87.
  • Rockwood DN, Preda RC, Yucel T, Wang X, Lovett ML, Kaplan DL. Materials fabrication from Bombyxmori silk fibroin. Nature Protocols. 2011; 6: 1612-1631.
  • Sah MK, Kumar A, Pramanik K. The extraction of fibroin protein from Bombyxmori silk cocoon: Optimizations of process parameters. International Journal of Bioinformatics Research. 2010; 2 (2): 33-41.
  • Kaplan DL, Mello CM, Arcidiacono S, Fossey S, Senecal K, Muller K. Editors. Protein-based Materials. Birkhauser. 1997:pp. 103-131.
  • Bini E, Knight DP, Kaplan DL. Mapping domain structures in silks from insects and spiders related to protein assembly. Journal of Molecular Biology.2004; 335 (1): 27-40.
  • Park TG. Degradation of poly(D, L-lactic acid) microspheres: Effect of molecular weight. Journal of Controlled Release.1994; 30: 161-173.
  • Zilberman M, Grinberg O. HRP-loaded bioresorbable microspheres: Effect of copolymer composition and molecular weight on microstructure and release profile. Journal of Biomaterials Applications.2008; 22 (5): 391-407.
  • Wenk E, Meinel AJ, Wildy S, Merkle HP, Meinel L. Microporous silk fibroin scaffolds embedding PLGA microparticles for controlled growth factor delivery in tissue engineering. Biomaterials. 2009; 30 (13): 2571-2581.
  • Trefiletti V, Conio G, Pioli F, Cavazza B, Perico A, Patrone E. The spinning of silk, 1: Molecular weight, Subunit structure, and Molecular shape of Bombyxmorifibroin. Makromolecular Chemistry.1980; 181: 1159-1179.
  • Cai K, Yao K, Lin S, Yang Z, Li X, Xie H, Qing T, Gao L. Poly(D, L-lactic acid) surfaces modified by silk fibroin: Effects on the culture of osteoblast in vitro. Biomaterials. 2002; 23 (4): 11531160.
  • Megeed Z, Cappello J, Ghandehari H. Genetically engineered silkelastinlike protein polymers for controlled drug delivery. Advanced Drug Delivery Reviews. 2002; 54 (8):1075-1091.
  • Asakura T, Kuzuhara A, Tabeta R, Saito H. Conformation characterization of Bombyxmori silk fibroin in the solid state by high-frequency 13C cross-polarization-magic angle spinning NMR, X-ray diffraction, and infrared spectroscopy. Macromolecules. 1985; 18: 1841-1845.
  • Jin HJ, Park J, Karageorgiou V, Kim UJ, Valluzzi R, Cebe P, Kaplan DL. Waterstable silk films with reduced beta-sheet content. Advanced Functional Materials.2005; 15:1241-1247.
  • Cappello J, Crissman J, Dorman M, Mikolajczak M, Textor G, Marquet M, Ferrari F. Genetic engineering of structural protein polymers. Biotechnology Progress.1990; 6 (3): 198-202.
  • Wang X, Wenk E, Matsumoto A, Meinel L, Li C, Kaplan DL. Silk microspheres for encapsulation and controlled release. Journal of Controlled Release.2007; 117 (3): 360-370.
  • Min BM, Jeong L, Lee KY, Park WH. Regenerated silk fibroin nanofibers: water vapour-induced structural changes and their effects on the behaviour of normal human cells. Macromolecular Bioscience.2006; 6 (4): 285-292.
  • Wenk E, Wandrey AJ, Merkle HP, Meinel L. Silk fibroin spheres as a platform for controlled drug delivery. Journal of Controlled Release.2008; 132 (1): 26-34.
  • Nakamura S, Magoshi J, Magoshi Y. Editors. Silk polymers: Materials Science and Biotechnology, ACS Symposium Series.1994; Vol. 544: pp. 211-221.
  • Li M, Lu S, Wu Z, Yan H, Mo J, Wang L. Study on porous silk fibroin materials. I. Fine structure of freeze dried silk fibroin. Journal of Applied Polymer Science.2001; 79: 2185-2191.
  • Nazarov R, Jin HJ, Kaplan DL. Porous 3D scaffolds from regenerated silk fibroin.Biomacromolecules.2004; 5 (3): 718-726.
  • Nam J, Park YH. Morphology of regenerated silk fibroin: Effects of freezing temperature, alcohol addition, and molecular weight. Journal of Applied Polymer Science.2001; 81:3008-3021.
  • Peppas NA, Khare AR. Preparation, structure and diffusional behaviour of hydrogels in controlled release. Advanced Drug Delivery Reviews. 1993; 11: 1-35.
  • Shaikh MM, Patil AS, Ajure PL, Lonikar SV. Starch-acrylic based hydrogel: Preparation and swelling characteristics. Research Journal of Science and Technology. 2014; 6 (2): 75-78.
  • Rujiravanit R, Kruaykitanon S, Jamieson AM, Tokura S. Preparation of crosslinked chitosan/silk fibroin blend films for drug delivery system. Macromolecular Biosciences. 2003; 3: 604611.
  • Garcia-Fuentes M, Giger E, Meinel L, Merkle HP. The effect of hyaluronic acid on silk fibroin conformation. Biomaterials. 2008; 29 (6): 633-642.
  • Gobin AS, Froude VE, Mathur AB. Structural and mechanical characteristics of silk fibroin and chitosan blend scaffolds for tissue regeneration. Journal of Biomedicals Materials Research A. 2005; 74 (3): 465-473.
  • Holland TA, Mikos AG. Biodegradable polymeric scaffolds. Improvements in bone tissue engineering through controlled drug delivery. Advancesin Biochemical Engineering/Biotechnology Journal.2006; 102: 161-185.
  • Lee SH, Shin H. Matrices and scaffolds for delivery of bioactive molecules in bone and cartilage tissue engineering. Advanced Drug Delivery Reviews.2007; 59 (4): 339-359.
  • Patel CM, Patel MA, Patel NP, Prajapati PH, Patel CN. Poly lactic glycolic acid (PLGA) as biodegradable polymer. Research Journal of Pharmacy and Technology. 2010; 3 (2): 353-360.
  • Kim UJ, Park J, Kim HJ, Wada M, Kaplan DL. Three-dimensional aqueous derived biomaterial scaffolds from silk fibroin. Biomaterials.2005; 26 (15): 2775-2785.
  • Khan MY, Gupta P, Verma VK. A Review – Biomedical engineering – Present and future prospective. 2013; 3 (4): 202-206.
  • Patel V, Akbari B, Deshmukh A, Goyani M, Patel A. A review on long acting PLGA based in situ forming micro particles formulation for a novel drug delivery dystem. Research Journal of Pharmaceutical Dosage Forms and Technology. 2016; 8 (2):127134.
  • Vepari CP, Kaplan DL. Covalently immobilized enzyme gradients within three-dimensional porous scaffolds. Biotechnology and Bioengineering. 2006; 93:1130-1137.
  • Wilz A, Pritchard EM, Li T, Lan JQ, Kaplan DL, Boison D. Silk polymer-based adenosine release: therapeutic potential for epilepsy. Biomaterials. 2008; 29:3609-3616.
  • Uebersax L, Mattotti M, Papaloizos M, Merkle HP, Gander B, Meinel L. Silk fibroin matrices for the controlled release of nerve growth factor (NGF). Biomaterials. 2007; 28: 4449-4460.
  • Quasim SZ, Ali MI, Irfan S, Naveed A. Advances in drug delivery system: Carbon nanotubes. Research Journal of Pharmacy and Technology. 2013; 6 (2): 75-79.
  • Uebersax L, Merkle HP, Meinel L. Insulin-like growth factor I releasing silk fibroin scaffolds induce chondrogenic differentiation of human mesenchymal stem cells. Journal of Controlled Release. 2008; 127:12-21.
  • Uebersax L, Fedele DE, Schumacher C, Kaplan DL, Merkle HP, Boison D, Meinel L. The support of adenosine release from adenosine kinase deficient ES cells by silk substrates. Biomaterials. 2006; 27:4599-4607.
  • Szybala C, Pritchard EM, Lusardi TA, Li T, Wilz A, Kaplan DL, Boison D. Antiepileptic effects of silk polymer based adenosine release in kindled rats. Experimental Neurology. 2009; 219: 126134.
  • Lu S, Wang X, Lu Q, Hu X, Uppal N, Omenetto FG, Kaplan DL. Stabilization of enzymes in silk films. Biomacromolecules. 2009; 10: 1032-1042.
  • Li C, Vepari C, Jin HJ, Kim HJ, Kaplan DL. Electrospun silkBMP-2 scaffolds for bone tissue engineering. Biomaterials. 2006; 27:3115-3124.
  • Verma C, Janghel A, Deo S, Raut P, Bhosle D, Kumar SS, Agrawal M, Amit N, Sharma M, Giri T, Tripathi DK, Ajazuddin, Alexander A. A comprehensive advancement on nanomedicines along with its various biomedical applications. 2015; 8 (7): 945957.
  • Kundu J, Chung YI, Kim YH, Tae G, Kundu SC. Silk fibroin nanoparticles for cellular uptake and control release. International Journal of Pharmaceutics. 2010; 388: 242-250.
  • Mandal BB, Kundu SC. Self-assembled silk sericin/poloxamer nanoparticles as nanocarriers of hydrophobic and hydrophilic drugs for targeted delivery. Nanotechnology. 2009; 20: 355101355111.
  • Wang X, Yucel T, Lu Q, Hu X, Kaplan DL. Silk nanospheres and microspheres from silk/PVA blend films for drug delivery. Biomaterials. 2010; 31: 1025-1035.
  • Wang X, Kim HJ, Xu P, Matsumoto A, Kaplan DL. Biomaterial coatings by stepwise deposition of silk fibroin. Langmuir. 2005; 21: 11335-11341.
  • Wang X, Wenk E, Hu X, Castro GR, Meinel L, Wang X, Li C, Merkle H, Kaplan DL. Silk coatings on PLGA and alginate microspheres for protein delivery. Biomaterials. 2007; 28: 41614169.
  • Wang X, Hu X, Daley A, Rabotyagova O, Cebe P, Kaplan DL. Nanolayer biomaterial coatings of silk fibroin for controlled release. Journal of Controlled Release. 2007; 121: 190-199.
  • Wang X, Zhang X, Castellot J, Herman I, Iafrati M, Kaplan DL. Controlled release from multilayer silk biomaterial coatings to modulate vascular cell responses. Biomaterials. 2008; 29:894-903.
  • Pritchard EM, Szybala C, Boison D, Kaplan DL. Silk fibroin encapsulated powder reservoirs for sustained release of adenosine. Journal of Controlled Release. 2010; 144 (2): 159-167.
  • Gangawane P, Sayed U. Dyeing of silk with discarded tetracycline hydrochloride drug. Asian Journal of Pharmacy and Technology. 2013; 3 (1): 34-36.
  • Singh D, Daharwal SJ, Rawat M. Hydrogels – A potent carter in wound healing. Research Journal of Pharmacy and Technology. 2008; 1 (1): 6-13.
  • Zhu B, Wang H, Leow WR, Cai Y, Loh XJ, Han MY, Chen X. Silk fibroin for flexible electronic devices. Advanced Materials. 2016; 28 (22): 4250-4265.
  • Radhika G, Sreelakshmi DP, Reddy PG, Venkatesh P, Reddy RK. An overview on regenerative medicine. Research Journal of Pharmacy and Technology. 2010; 3 (3): 727-728.

Abstract Views: 202

PDF Views: 0




  • Silk Fibroin:A Boon to Pharmaceutical and Biomedical Applications

Abstract Views: 202  |  PDF Views: 0

Authors

Kiran R. Birajdar
Department of Pharmaceutics, STES’s Sinhgad College of Pharmacy, Vadgaon (Bk.), Pune - 411041 (M.S.), India
Satish K. Mandlik
Department of Pharmaceutics, STES’s Sinhgad College of Pharmacy, Vadgaon (Bk.), Pune - 411041 (M.S.), India

Abstract


Silks are naturally occurring polymers that have been used clinically as sutures for centuries. When naturally extruded from insects or worms, silk is composed of a filament core protein, termed fibroin. To date fibroin from Bombyxmori silk worm has been the dominant source for silk-based biomaterials studied. Silk fibroin (SF) is a naturally occurring protein polymer with several unique properties that make it a suitable material for incorporation into a variety of drug delivery vehicles capable of delivering a range of therapeutic agents. SF is biocompatible, slowly biodegradable, and endowed with excellent mechanical properties and process ability. So far, the main focus of SF drug delivery systems has been on tissue regeneration applications. For instance, growth factor loaded SF scaffolds were suggested for the tissue engineering of bone and cartilage, as well as for vascular and nerve regeneration devices and wound healing products. Moreover, SF matrices were proposed for oral, transmucosal and ocular drug delivery. SF matrices have been shown to successfully deliver anticancer drugs, small molecules, and biomolecules. This article will provide an in-depth discussion on the SF properties and pharmaceutical and drug delivery applications of Silk fibroin in nanoparticles.

Keywords


Silk, Silk Fibroin, Bombyxmori, Pharmaceuticals, Drug Delivery.

References