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Thiolated chitosan microparticles: a vehicle for nasal peptide drug delivery.
Int J Pharm. 2006 Jan 13; 307(2):270-7.IJ

Abstract

The goal of this study was to develop a microparticulate delivery system based on a thiolated chitosan conjugate for the nasal application of peptides. Insulin was used as model peptide. For thiolation of chitosan 2-iminothiolane was covalently linked to chitosan. The resulting chitosan-TBA (chitosan-4-thiobutylamidine) conjugate featured 304.89+/-63.45 micromol thiol groups per gram polymer. 6.5% of these thiol groups were oxidised. A mixture of the chitosan-TBA conjugate, insulin and the permeation mediator reduced glutathione were formulated to microparticles. Control microparticles comprised unmodified chitosan and insulin. As second control served mannitol-insulin microparticles. All microparticulate systems were prepared via the emulsification solvent evaporation technique. In 100 mM phosphate buffer pH 6.8 chitosan-TBA-insulin microparticles swelled 4.39+/-0.52-fold in size, whereas chitosan based microparticles did not swell at all. Chitosan-TBA microparticles showed a controlled release of fluorescein isothiocyanate (FITC)-labelled insulin over 6 h. Nasal administered chitosan-TBA-insulin microparticles led to an absolute bioavailability of 7.24+/-0.76% (means+/-S.D.; n=3) in conscious rats. In contrast, chitosan-insulin microparticles and mannitol-insulin microparticles exhibited an absolute bioavailability of 2.04+/-1.33% and 1.04+/-0.27%, respectively (means+/-S.D.; n=4). Because of these results microparticles comprising chitosan-TBA and reduced glutathione seem to represent a useful formulation for the nasal administration of peptides.

Authors+Show Affiliations

Institute of Pharmaceutical Technology and Biopharmaceutics, Center of Pharmacy, University of Vienna, A-1090 Vienna, Austria.No affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16300914

Citation

Krauland, Alexander H., et al. "Thiolated Chitosan Microparticles: a Vehicle for Nasal Peptide Drug Delivery." International Journal of Pharmaceutics, vol. 307, no. 2, 2006, pp. 270-7.
Krauland AH, Guggi D, Bernkop-Schnürch A. Thiolated chitosan microparticles: a vehicle for nasal peptide drug delivery. Int J Pharm. 2006;307(2):270-7.
Krauland, A. H., Guggi, D., & Bernkop-Schnürch, A. (2006). Thiolated chitosan microparticles: a vehicle for nasal peptide drug delivery. International Journal of Pharmaceutics, 307(2), 270-7.
Krauland AH, Guggi D, Bernkop-Schnürch A. Thiolated Chitosan Microparticles: a Vehicle for Nasal Peptide Drug Delivery. Int J Pharm. 2006 Jan 13;307(2):270-7. PubMed PMID: 16300914.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Thiolated chitosan microparticles: a vehicle for nasal peptide drug delivery. AU - Krauland,Alexander H, AU - Guggi,Davide, AU - Bernkop-Schnürch,Andreas, Y1 - 2005/11/18/ PY - 2005/07/04/received PY - 2005/09/27/revised PY - 2005/10/15/accepted PY - 2005/11/23/pubmed PY - 2006/3/17/medline PY - 2005/11/23/entrez SP - 270 EP - 7 JF - International journal of pharmaceutics JO - Int J Pharm VL - 307 IS - 2 N2 - The goal of this study was to develop a microparticulate delivery system based on a thiolated chitosan conjugate for the nasal application of peptides. Insulin was used as model peptide. For thiolation of chitosan 2-iminothiolane was covalently linked to chitosan. The resulting chitosan-TBA (chitosan-4-thiobutylamidine) conjugate featured 304.89+/-63.45 micromol thiol groups per gram polymer. 6.5% of these thiol groups were oxidised. A mixture of the chitosan-TBA conjugate, insulin and the permeation mediator reduced glutathione were formulated to microparticles. Control microparticles comprised unmodified chitosan and insulin. As second control served mannitol-insulin microparticles. All microparticulate systems were prepared via the emulsification solvent evaporation technique. In 100 mM phosphate buffer pH 6.8 chitosan-TBA-insulin microparticles swelled 4.39+/-0.52-fold in size, whereas chitosan based microparticles did not swell at all. Chitosan-TBA microparticles showed a controlled release of fluorescein isothiocyanate (FITC)-labelled insulin over 6 h. Nasal administered chitosan-TBA-insulin microparticles led to an absolute bioavailability of 7.24+/-0.76% (means+/-S.D.; n=3) in conscious rats. In contrast, chitosan-insulin microparticles and mannitol-insulin microparticles exhibited an absolute bioavailability of 2.04+/-1.33% and 1.04+/-0.27%, respectively (means+/-S.D.; n=4). Because of these results microparticles comprising chitosan-TBA and reduced glutathione seem to represent a useful formulation for the nasal administration of peptides. SN - 0378-5173 UR - https://www.unboundmedicine.com/medline/citation/16300914/Thiolated_chitosan_microparticles:_a_vehicle_for_nasal_peptide_drug_delivery_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(05)00673-3 DB - PRIME DP - Unbound Medicine ER -