Chitosan nanoparticles: a promising system in novel drug delivery.

The ability of nanoparticles to manipulate the molecules and their structures has revolutionized the conventional drug delivery system. The chitosan nanoparticles, because of their biodegradability, biocompatibility, better stability, low toxicity, simple and mild preparation methods, offer a valuable tool to novel drug delivery systems in the present scenario. Besides ionotropic gelation method, other methods such as microemulsion method, emulsification solvent diffusion method, polyelectrolyte complex method, emulsification cross-linking method, complex coacervation method and solvent evaporation method are also in use. The chitosan nanoparticles have also been reported to have key applications in parentral drug delivery, per-oral administration of drugs, in non-viral gene delivery, in vaccine delivery, in ocular drug delivery, in electrodeposition, in brain targeting drug delivery, in stability improvement, in mucosal drug delivery in controlled drug delivery of drugs, in tissue engineering and in the effective delivery of insulin. The present review describes origin and properties of chitosan and its nanoparticles along with the different methods of its preparation and the various areas of novel drug delivery where it has got its application.

[1]  Mohamed H. El-Shabouri,et al.  Positively charged nanoparticles for improving the oral bioavailability of cyclosporin-A. , 2002, International journal of pharmaceutics.

[2]  W. Tiyaboonchai,et al.  Formulation and characterization of amphotericin B-chitosan-dextran sulfate nanoparticles. , 2007, International journal of pharmaceutics.

[3]  Miqin Zhang,et al.  Chitosan and lactic acid-grafted chitosan nanoparticles as carriers for prolonged drug delivery , 2006, International journal of nanomedicine.

[4]  R. Jain,et al.  Microvascular permeability of normal and neoplastic tissues. , 1986, Microvascular research.

[5]  Manisha Chawla,et al.  Chitosan: some pharmaceutical and biological aspects ‐ an update , 2001, The Journal of pharmacy and pharmacology.

[6]  S. Aiba Studies on chitosan: 4. Lysozymic hydrolysis of partially N-acetylated chitosans. , 1992, International journal of biological macromolecules.

[7]  B. Sarmento,et al.  Alginate/Chitosan Nanoparticles are Effective for Oral Insulin Delivery , 2007, Pharmaceutical Research.

[8]  L. Illum,et al.  Chitosan as a nasal delivery system: evaluation of insulin absorption enhancement and effect on nasal membrane integrity using rat models , 1996 .

[9]  M. Alonso,et al.  Evaluation of cationic polymer-coated nanocapsules as ocular drug carriers , 1997 .

[10]  J. Tsibouklis,et al.  Polymeric microspheres for drug delivery to the oral cavity: an in vitro evaluation of mucoadhesive potential. , 2003, Journal of pharmaceutical sciences.

[11]  T. Kissel,et al.  The depolymerization of chitosan: effects on physicochemical and biological properties. , 2004, International journal of pharmaceutics.

[12]  G. Lee Microparticulate systems for the delivery of proteins and vaccines , 1997 .

[13]  P Couvreur,et al.  Development of a new drug carrier made from alginate. , 1993, Journal of pharmaceutical sciences.

[14]  B Larijani,et al.  Permeation enhancer effect of chitosan and chitosan derivatives: comparison of formulations as soluble polymers and nanoparticulate systems on insulin absorption in Caco-2 cells. , 2008, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[15]  M. Davies,et al.  Atomic force microscopy of gastric mucin and chitosan mucoadhesive systems. , 2000, The Biochemical journal.

[16]  H E Junginger,et al.  Chitosan for mucosal vaccination. , 2001, Advanced drug delivery reviews.

[17]  V. Dodane,et al.  Effect of chitosan on epithelial permeability and structure. , 1999, International journal of pharmaceutics.

[18]  J. Lehoux,et al.  Some effects of chitosan on liver function in the rat. , 1993, Endocrinology.

[19]  S. Davis,et al.  Evaluation of bioadhesive polymers as delivery systems for nose to brain delivery: in vitro characterisation studies. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[20]  P. G. Seferian,et al.  Immune stimulating activity of two new chitosan containing adjuvant formulations. , 2000, Vaccine.

[21]  V. Parameswaran,et al.  Potential use of chitosan nanoparticles for oral delivery of DNA vaccine in Asian sea bass (Lates calcarifer) to protect from Vibrio (Listonella) anguillarum. , 2008, Fish & shellfish immunology.

[22]  C. Fong,et al.  Transfection efficiency of chitosan vectors: effect of polymer molecular weight and degree of deacetylation. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[23]  Stefaan C. De Smedt,et al.  Cationic Polymer Based Gene Delivery Systems , 2000, Pharmaceutical Research.

[24]  Feng Xu,et al.  Three-dimensional polymeric systems for cancer cell studies , 2007, Cytotechnology.

[25]  C. Remuñán-López,et al.  Enhancement of Nasal Absorption of Insulin Using Chitosan Nanoparticles , 1999, Pharmaceutical Research.

[26]  Y Wang,et al.  Chitosan-DNA nanoparticles as gene carriers: synthesis, characterization and transfection efficiency. , 2001, Journal of controlled release : official journal of the Controlled Release Society.

[27]  Yu-Hsin Lin,et al.  Preparation and characterization of nanoparticles shelled with chitosan for oral insulin delivery. , 2007, Biomacromolecules.

[28]  I. Vural,et al.  Preparation and In Vitro Evaluation of bFGF-Loaded Chitosan Nanoparticles , 2007, Drug delivery.

[29]  H. Junginger,et al.  Intestinal Absorption of Octreotide Using Trimethyl Chitosan Chloride: Studies in Pigs , 2001, Pharmaceutical Research.

[30]  Y. Ikada,et al.  Positively charged gelatin microspheres as gastric mucoadhesive drug delivery system for eradication of H. pylori. , 2000, Drug delivery.

[31]  Sinjan De,et al.  Polymer relationships during preparation of chitosan-alginate and poly-l-lysine-alginate nanospheres. , 2003, Journal of controlled release : official journal of the Controlled Release Society.

[32]  G. Luo,et al.  Adsorption of diuretic furosemide onto chitosan nanoparticles prepared with a water-in-oil nanoemulsion system , 2005 .

[33]  K. Leong,et al.  Chitosan nanoparticles for oral drug and gene delivery , 2006, International journal of nanomedicine.

[34]  M. Alonso,et al.  Efficacy and Mechanism of Action of Chitosan Nanocapsules for Oral Peptide Delivery , 2006, Pharmaceutical Research.

[35]  W. Park,et al.  Blood compatibility and biodegradability of partially N-acylated chitosan derivatives. , 1995, Biomaterials.

[36]  K. Leong,et al.  The effect of the degree of chitosan deacetylation on the efficiency of gene transfection. , 2004, Biomaterials.

[37]  Lisbeth Illum,et al.  Effect of Chitosan on the Permeability of Monolayers of Intestinal Epithelial Cells (Caco-2) , 1994, Pharmaceutical Research.

[38]  E. Leo,et al.  Chitosan-Alginate Microparticles as a Protein Carrier , 2001, Drug development and industrial pharmacy.

[39]  H E Junginger,et al.  Trimethylated chitosan as polymeric absorption enhancer for improved peroral delivery of peptide drugs. , 2004, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[40]  Bruno Sarmento,et al.  Characterization of insulin-loaded alginate nanoparticles produced by ionotropic pre-gelation through DSC and FTIR studies , 2006 .

[41]  A. Perkins,et al.  Evaluation of the clearance characteristics of bioadhesive systems in humans. , 1999, International journal of pharmaceutics.

[42]  B. Sarmento,et al.  Development and Comparison of Different Nanoparticulate Polyelectrolyte Complexes as Insulin Carriers , 2006, International Journal of Peptide Research and Therapeutics.

[43]  M. Alonso,et al.  Novel hydrophilic chitosan‐polyethylene oxide nanoparticles as protein carriers , 1997 .

[44]  V. Dodane,et al.  Pharmaceutical applications of chitosan , 1998 .

[45]  F. Hoppe-Seyler Ueber Chitin und Cellulose , 1894 .

[46]  H E Junginger,et al.  Chitosan and its derivatives in mucosal drug and vaccine delivery. , 2001, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[47]  G. Payne,et al.  Chitosan-mediated and spatially selective electrodeposition of nanoscale particles. , 2005, Langmuir : the ACS journal of surfaces and colloids.

[48]  R. Müller Colloidal Carriers for Controlled Drug Delivery and Targeting: Modification, Characterization, and In Vivo Distribution , 1991 .

[49]  Per Artursson,et al.  Chitosans as Absorption Enhancers for Poorly Absorbable Drugs. 1: Influence of Molecular Weight and Degree of Acetylation on Drug Transport Across Human Intestinal Epithelial (Caco-2) Cells , 1996, Pharmaceutical Research.

[50]  R. Bodmeier,et al.  A Novel Approach to the Oral Delivery of Micro- or Nanoparticles , 1989, Pharmaceutical Research.

[51]  Rakesh K. Sharma,et al.  Pharmacoscintigraphic evaluation of polysorbate80-coated chitosan nanoparticles for brain targeting , 2005 .

[52]  S. Davis,et al.  Chitosan as a novel nasal delivery system for vaccines. , 2001, Advanced drug delivery reviews.

[53]  R. Chen,et al.  Cavitation effects versus stretch effects resulted in different size and polydispersity of ionotropic gelation chitosan-sodium tripolyphosphate nanoparticle , 2008 .

[54]  Y. Murata,et al.  Preparation of alginate gel beads containing chitosan nicotinic acid salt and the functions. , 1999, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[55]  Hui Xu,et al.  Bioadhesive polysaccharide in protein delivery system: chitosan nanoparticles improve the intestinal absorption of insulin in vivo. , 2002, International journal of pharmaceutics.

[56]  Tao Wang,et al.  Modulation of surface charge, particle size and morphological properties of chitosan-TPP nanoparticles intended for gene delivery. , 2005, Colloids and surfaces. B, Biointerfaces.

[57]  M. Alonso,et al.  Chitosan and Chitosan/Ethylene Oxide-Propylene Oxide Block Copolymer Nanoparticles as Novel Carriers for Proteins and Vaccines , 1997, Pharmaceutical Research.

[58]  S. Neau,et al.  In vitro degradation of chitosan by bacterial enzymes from rat cecal and colonic contents. , 2002, Biomaterials.

[59]  A. Bozkır,et al.  Chitosan Nanoparticles for Plasmid DNA Delivery: Effect of Chitosan Molecular Structure on Formulation and Release Characteristics , 2004, Drug delivery.

[60]  P. Couvreur,et al.  Actinomycin D absorbed on polymethylcyanoacrylate nanoparticles: increased efficiency against an experimental tumor. , 1980, European journal of cancer.

[61]  T. Bettinger,et al.  Chitosan-Based Vector/DNA Complexes for Gene Delivery: Biophysical Characteristics and Transfection Ability , 1998, Pharmaceutical Research.

[62]  S. Neau,et al.  In vitro degradation of chitosan by a commercial enzyme preparation: effect of molecular weight and degree of deacetylation. , 2001, Biomaterials.

[63]  A. M. Dyer,et al.  Nasal Delivery of Insulin Using Novel Chitosan Based Formulations: A Comparative Study in Two Animal Models Between Simple Chitosan Formulations and Chitosan Nanoparticles , 2002, Pharmaceutical Research.

[64]  Haliza Katas,et al.  Development and characterisation of chitosan nanoparticles for siRNA delivery. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[65]  J. Kreuter,et al.  Colloidal Drug Delivery Systems , 1994 .

[66]  Jayanth Panyam,et al.  Surfactant-polymer Nanoparticles: A Novel Platform for Sustained and Enhanced Cellular Delivery of Water-soluble Molecules , 2007, Pharmaceutical Research.

[67]  K. Janes,et al.  Chitosan nanoparticles as delivery systems for doxorubicin. , 2001, Journal of controlled release : official journal of the Controlled Release Society.

[68]  H. Tønnesen,et al.  Alginate in Drug Delivery Systems , 2002, Drug development and industrial pharmacy.

[69]  O. Kayser,et al.  The impact of nanobiotechnology on the development of new drug delivery systems. , 2005, Current pharmaceutical biotechnology.

[70]  M. Tabrizian,et al.  Effect of experimental parameters on the formation of alginate–chitosan nanoparticles and evaluation of their potential application as DNA carrier , 2005, Journal of biomaterials science. Polymer edition.

[71]  Rajesh Pandey,et al.  Nano-encapsulation of azole antifungals: potential applications to improve oral drug delivery. , 2005, International journal of pharmaceutics.

[72]  M. Rafiee-Tehrani,et al.  Preparation, characterization and antibacterial activities of chitosan, N-trimethyl chitosan (TMC) and N-diethylmethyl chitosan (DEMC) nanoparticles loaded with insulin using both the ionotropic gelation and polyelectrolyte complexation methods. , 2008, International journal of pharmaceutics.

[73]  Shirui Mao,et al.  Effect of chitosan structure properties and molecular weight on the intranasal absorption of tetramethylpyrazine phosphate in rats. , 2008, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[74]  V. Sinha,et al.  Evaluation of mucoadhesive properties of chitosan microspheres prepared by different methods , 2004, AAPS PharmSciTech.

[75]  Robert Gurny,et al.  Topical use of chitosan in ophthalmology: tolerance assessment and evaluation of precorneal retention. , 1999, International journal of pharmaceutics.

[76]  B. Sarmento,et al.  Insulin-loaded nanoparticles are prepared by alginate ionotropic pre-gelation followed by chitosan polyelectrolyte complexation. , 2007, Journal of nanoscience and nanotechnology.

[77]  A. Vila,et al.  Design of biodegradable particles for protein delivery. , 2002, Journal of controlled release : official journal of the Controlled Release Society.

[78]  R. Pandey,et al.  Polymer based drug delivery systems for mycobacterial infections. , 2004, Current drug delivery.

[79]  K. Leong,et al.  DNA-polycation nanospheres as non-viral gene delivery vehicles. , 1998, Journal of controlled release : official journal of the Controlled Release Society.

[80]  C. Cho,et al.  Galactosylated chitosan-graft-dextran as hepatocyte-targeting DNA carrier. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[81]  T. Okano,et al.  Time-programmed pulsatile release of dextran from calcium-alginate gel beads coated with carboxy-n-propylacrylamide copolymers. , 2002, Journal of controlled release : official journal of the Controlled Release Society.

[82]  Xiaojun Ma,et al.  The enzymatic degradation and swelling properties of chitosan matrices with different degrees of N-acetylation. , 2005, Carbohydrate research.

[83]  F. Wang,et al.  Designing chitosan-dextran sulfate nanoparticles using charge ratios , 2007, AAPS PharmSciTech.

[84]  Maria José Alonso,et al.  Comparative Uptake Studies of Bioadhesive and Non-Bioadhesive Nanoparticles in Human Intestinal Cell Lines and Rats: The Effect of Mucus on Particle Adsorption and Transport , 2002, Pharmaceutical Research.

[85]  K. Leong,et al.  Interactions of phospholipid bilayer with chitosan: effect of molecular weight and pH. , 2001, Biomacromolecules.

[86]  P. Bhat,et al.  The limiting role of mucus in drug absorption : drug permeation through mucus solution , 1995 .

[87]  A. Vila,et al.  Low molecular weight chitosan nanoparticles as new carriers for nasal vaccine delivery in mice. , 2004, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[88]  R. Pandey,et al.  Alginate nanoparticles as antituberculosis drug carriers: formulation development, pharmacokinetics and therapeutic potential. , 2006, The Indian journal of chest diseases & allied sciences.

[89]  J. Hamman,et al.  Evaluation of the Mucoadhesive Properties of N-Trimethyl Chitosan Chloride , 2003, Drug development and industrial pharmacy.

[90]  L. Shi,et al.  Adsorption of Neutral Proteinase on Chitosan Nano-Particles , 2007 .

[91]  J. Mano,et al.  Chitosan-Based Particles as Controlled Drug Delivery Systems , 2004, Drug delivery.

[92]  Yoshiaki,et al.  Preparations of biodegradable nanospheres of water-soluble and insoluble drugs with D, L-lactide/glycolide copolymer by a novel spontaneous emulsification solvent diffusion method, and the drug release behavior. , 1993 .

[93]  Y. Ikada,et al.  Macrophage phagocytosis of biodegradable microspheres composed of L-lactic acid/glycolic acid homo- and copolymers. , 1988, Journal of biomedical materials research.

[94]  Yan Chen,et al.  Chitosan-dextran sulfate nanoparticles for delivery of an anti-angiogenesis peptide , 2003, Letters in Peptide Science.

[95]  Harjinder Singh,et al.  Preparation and characterization of nanoparticles formed by chitosan-caseinate interactions. , 2008, Colloids and surfaces. B, Biointerfaces.

[96]  R. Muzzarelli Chitosan-based dietary foods , 1996 .

[97]  T. Okano,et al.  Cell sheet engineering for myocardial tissue reconstruction. , 2003, Biomaterials.

[98]  Hans E. Junginger,et al.  Mucoadhesive Polymers in Peroral Peptide Drug Delivery. VI. Carbomer and Chitosan Improve the Intestinal Absorption of the Peptide Drug Buserelin In Vivo , 1996, Pharmaceutical Research.

[99]  S. Hirota,et al.  Effect of liposomalization on the antitumor activity, side-effects and tissue distribution of CPT-11. , 1998, Cancer letters.

[100]  Krishnendu Roy,et al.  Oral gene delivery with chitosan–DNA nanoparticles generates immunologic protection in a murine model of peanut allergy , 1999, Nature Medicine.