Abstract
Therapeutic proteins represent a significant part of the new pharmaceuticals coming on the market every year and are now widely spread in therapy to treat or relief symptoms related to many metabolic and oncologic diseases. The parenteral route remains as a primary strategy for protein administration essentially due to its specific physicochemical properties. However, the research on alternative nonparenteral delivery routes continues. The high molecular weight (MW), hydrophilicity, and charged nature of therapeutically valued proteins render transport through membranes very difficult. In this regard, chitosan arises as a promising candidate for the development of protein-containing drug formulations, due to its exceptional biological properties. Chitosan-based delivery systems have been proposed as valid approaches to provide protective conditions to proteins from denaturation and loss of activity, during preparation and delivery, as well as during long-term storage of the prepared formulation.
In this chapter, one production method of a chitosan-based nanoparticle formulation is presented, as well as several characterization techniques to assess both nanoparticles and proteins characteristics and stability.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Frokjaer S, Otzen DE (2005) Protein drug stability: a formulation challenge. Nat Rev Drug Discov 4:298–306
Antosova Z, Mackova M, Kral V, Macek T (2009) Therapeutic application of peptides and proteins: parenteral forever? Trends Biotechnol 27:628–635
Lien S, Lowman HB (2003) Therapeutic peptides. Trends Biotechnol 21:556–562
Mahmood I (2008) Methods to determine pharmacokinetic profiles of therapeutic proteins. Drug Discov Today Technol 5:e65–e69
Cryan S-A (2005) Carrier-based strategies for targeting protein and peptide drugs to the lungs. AAPS J 7:E20–E41
Lee HJ (2002) Protein drug oral delivery: the recent progress. Arch Pharm Res 25:572–584
Morishita M, Peppas NA (2006) Is the oral route possible for peptide and protein drug delivery? Drug Discov Today 11:905–910
Amidi M, Mastrobattista E, Jiskoot W, Hennink WE (2010) Chitosan-based delivery systems for protein therapeutics and antigens. Adv Drug Deliv Rev 62:59–82
Shih C-M, Shieh Y-T, Twu Y-K (2009) Preparation and characterization of cellulose/chitosan blend films. Carbohydr Polym 78:169–174
Sinha VR, Singla AK, Wadhawan S, Kaushik R, Kumria R, Bansal K, Dhawan S (2004) Chitosan microspheres as a potential carrier for drugs. Int J Pharm 274:1–33
George M, Abraham TE (2006) Polyionic hydrocolloids for the intestinal delivery of protein drugs: alginate and chitosan—a review. J Control Rel 114:1–14
Rinaudo M (2006) Chitin and chitosan: properties and applications. Prog Polym Sci 31:603–632
Alonso MJ, Sánchez A (2003) The potential of chitosan in ocular drug delivery. J Pharm Pharmacol 55:1451–1463
Fernandez-Saiz P, Lagaron JM, Ocio MJ (2009) Optimization of the film-forming and storage conditions of chitosan as an antimicrobial agent. J Agric Food Chem 57:3298–3307
Tomida H, Fujii T, Furutani N, Michihara A, Yasufuku T, Akasaki K, Maruyama T, Otagiri M, Gebicki JM, Anraku M (2009) Antioxidant properties of some different molecular weight chitosans. Carbohydr Polym 344:1690–1696
Sashiwa H, Aiba SI (2004) Chemically modified chitin and chitosan as biomaterials. Prog Polym Sci (Oxford) 29:887–908
Fonte P, Nogueira T, Gehm C, Ferreira D, Sarmento B (2011) Chitosan-coated solid lipid nanoparticles enhance the oral absorption of insulin. Drug Deliv Translational Res 1(4):299–308
Shi Y, Huang G (2009) Recent developments of biodegradable and biocompatible materials based micro/nanoparticles for delivering macromolecular therapeutics. Crit Rev Ther Drug Carrier Syst 26:29–84
Zhao QS, Ji QX, Xing K, Li XY, Liu CS, Chen XG (2009) Preparation and characteristics of novel porous hydrogel films based on chitosan and glycerophosphate. Carbohydr Polym 76:410–416
Huang X, Du Y-Z, Yuan H, Hu F-Q (2009) Preparation and pharmacodynamics of low-molecular-weight chitosan nanoparticles containing insulin. Carbohydr Polym 76:368–373
Andrade F, Antunes F, Nascimento AV, da Silva SB, das Neves J, Ferreira D, Sarmento B (2011) Chitosan formulations as carriers for therapeutic proteins. Curr Drug Discov Technol 8(3):157–172
Gan Q, Wang T (2007) Chitosan nanoparticle as protein delivery carrier–systematic examination of fabrication conditions for efficient loading and release. Colloids Surf B Biointerfaces 59:24–34
Thanou M, Verhoef JC, Marbach P, Junginger HE (2000) Intestinal absorption of octreotide: N-trimethyl chitosan chloride (TMC) ameliorates the permeability and absorption properties of the somatostatin analogue in vitro and in vivo. J Pharm Sci 89:951–957
Thanou M, Verhoef JC, Verheijden JH, Junginger HE (2001) Intestinal absorption of octreotide using trimethyl chitosan chloride: studies in pigs. Pharm Res 18:823–828
Van Der Merwe SM, Verhoef JC, Verheijden JHM, Kotzé AF, Junginger HE (2004) Trimethylated chitosan as polymeric absorption enhancer for improved peroral delivery of peptide drugs. Eur J Pharm Biopharm 58:225–235
Qian F, Cui F, Ding J, Tang C, Yin C (2006) Chitosan graft copolymer nanoparticles for oral protein drug delivery: preparation and characterization. Biomacromolecules 7:2722–2727
Sarmento B, Martins S, Ribeiro A, Veiga F, Neufeld R, Ferreira D (2006) Development and comparison of different nanoparticulate polyelectrolyte complexes as insulin carriers. Int J Pept Res Ther 12:131–138
Sarmento B, Ribeiro A, Veiga F, Sampaio P, Neufeld R, Ferreira D (2007) Alginate/chitosan nanoparticles are effective for oral insulin delivery. Pharm Res 24:2198–2206
Sarmento B, Ribeiro A, Veiga F, Ferreira D, Neufeld R (2007) Oral bioavailability of insulin contained in polysaccharide nanoparticles. Biomacromolecules 8:3054–3060
Yamamoto H, Kuno Y, Sugimoto S, Takeuchi H, Kawashima Y (2005) Surface-modified PLGA nanosphere with chitosan improved pulmonary delivery of calcitonin by mucoadhesion and opening of the intercellular tight junctions. J Control Release 102:373–381
Makhlof A, Werle M, Tozuka Y, Takeuchi H (2010) Nanoparticles of glycol chitosan and its thiolated derivative significantly improved the pulmonary delivery of calcitonin. Int J Pharm 397:92–95
Prego C, García M, Torres D, Alonso MJ (2005) Transmucosal macromolecular drug delivery. J Control Release 101:151–162
Hall JB, Dobrovolskaia MA, Patri AK, McNeil SE (2007) Characterization of nanoparticles for therapeutics. Nanomedicine (Lond) 2:789–803
Peltonen L, Hirvonen J (2008) Physicochemical characterization of nano- and microparticles. Curr Nanosci 4:101–107
Van de Weert M, Hering JA, Haris PI (2005) Fourier transform infrared spectroscopy. In: Jiskoot W, Crommelin D (eds) Methods for structural analysis of protein pharmaceuticals. AAPS, Arlington, VA, pp 131–166
Jørgensen L, Vermehren C, Bjerregaard S, Froekjaer S (2003) Secondary structure alterations in insulin and growth hormone water-in-oil emulsions. Int J Pharm 254:7–10
Kelly SM, Jess TJ, Price NC (2005) How to study proteins by circular dichroism. Biochim Biophys Acta (BBA)—Proteins Proteomics 1751:119–139
Sarmento B, Ribeiro AJ, Veiga F, Ferreira DC, Neufeld RJ (2007) Insulin-loaded nanoparticles are prepared by alginate ionotropic pre-gelation followed by chitosan polyelectrolyte complexation. J Nanosci Nanotechnol 7:2833–2841
Sarmento B, Ferreira D, Jorgensen L, van de Weert M (2007) Probing insulin’s secondary structure after entrapment into alginate/chitosan nanoparticles. Eur J Pharm Biopharm 65:10–17
Acknowledgments
The authors acknowledge the financial support from Fundação para a Ciência e a Tecnologia, Portugal (PTDC/SAU-FCF/104492/2008).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Fonte, P., Andrade, J.C., Seabra, V., Sarmento, B. (2012). Chitosan-Based Nanoparticles as Delivery Systems of Therapeutic Proteins. In: Voynov, V., Caravella, J. (eds) Therapeutic Proteins. Methods in Molecular Biology, vol 899. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-921-1_28
Download citation
DOI: https://doi.org/10.1007/978-1-61779-921-1_28
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-61779-920-4
Online ISBN: 978-1-61779-921-1
eBook Packages: Springer Protocols