Preparation and Characterization of Chitosan-Insulin-Tripolyphosphate Membrane for Controlled Drug Release: Effect of Cross Linking Agent

DOI: 10.4236/jbnb.2014.54025   PDF   HTML     4,654 Downloads   5,714 Views   Citations


The term Diabetes Mellitus (DM) comprises a group of metabolic disorders characterized by chronic hyperglycemia resulting from defects in the secretion and/or action of insulin. The Insulin therapy constitutes the preferred treatment for DM, consisting of daily subcutaneous insulin injections to control blood glucose levels. The chitosan studied for Biomedicine is a biomaterial that can be used for controlled release of drugs whose release rate can be controlled by Sodium Tripolyphosphate (TPP), which is an ionic cross linker of the chitosan. Present study, therefore, was aimed to develop and evaluate membranes of chitosan and chitosan cross linked by TPP for use in controlled release of insulin system, with the purpose of obtaining an alternative to the injectable administration of this drug. The developed membranes were characterized by the techniques of Fourier Transform Infrared spectroscopy (FTIR), Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDX), High Performance Liquid Chromatography (HPLC) and Evaluation of Cell Viability of Macrophages (MTT). With the FTIR technique the interaction between chitosan, tripolyphosphate and insulin was identified. Chemical elements present in chitosan, insulin and sodium tripolyphosphate membranes were detected by EDX technique. By SEM technique, the changes in the morphology of the membrane containing insulin, with the presence of granular particles of varying sizes, could be observed when compared to pure chitosan. With HPLC assay insulin was identified and it was shown that it gets separated from chitosan membrane even when the membrane was cross linked by the TPP, though at a reduced rate. The crosslinking agent was effective to control the rate of insulin release. The biocompatibility of the prepared membranes was confirmed by cell viability of macrophages using the MTT assay. The developed membranes, therefore, have potential for use as a biomaterial in controlled release systems for insulin.

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Lima, H. , Lia, F. and Ramdayal, S. (2014) Preparation and Characterization of Chitosan-Insulin-Tripolyphosphate Membrane for Controlled Drug Release: Effect of Cross Linking Agent. Journal of Biomaterials and Nanobiotechnology, 5, 211-219. doi: 10.4236/jbnb.2014.54025.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] WHO (2008) The Global Burden of Disease (2004 Update).
[2] Khafagy, E.-S., Morishita, M., Onuki, Y. and Takayama, K. (2007) Current Challenges in Non-Invasive Insulin Delivery Systems: A Comparative Review. Advanced Drug Delivery Reviews, 59, 1521-1546.
[3] Rios, M. (2005) Polymers for Controlled Release: Formulation Follows Function. Pharmaceutical Technology, 29, 42-50.
[4] Vilar, G., Tulla-Puche, J. and Alberício, F. (2012) Polymers and Drug Delivery Systems. Current Drug Delivery, 9, 1-27.
[5] Calvo, P., Remuñàn-Lopez, C., Vila-Jato, J.L. and Alonso, M.J. (1997) Chitosan and Chitosan/Ethylene Oxide-Propylene Oxide Block Copolymer Nanoparticles as Novel Carriers for Proteins and Vaccines. Pharmaceutical Research 14, 1431-1436.
[6] Osorio, S.M.L. (2007) Novel Polymeric Systems Based on Natural Materials: Development and Biological Performance. Master Dissertation, Escola de Engenharia, Universidade do Minho, Braga.
[7] Boonsongrit, Y., Mueller, B.W. and Mitrejev, A. (2008) Characterization of Drug-Chitosan Interaction by 1H NMR, FTIR and Isothermal Titration Calorimetry. European Journal of Pharmaceutics and Biopharmaceutics, 69, 388-395.
[8] Xua, X., Yao Fua, X., Hua, H., Duanb, Y. and Zhang, Z. (2006) Quantitative Determination of Insulin Entrapment Efficiency in Triblock Copolymeric Nanoparticles by High-Performance Liquid Chromatography. Journal of Pharmaceutical and Biomedical Analysis, 41, 266-273.
[9] Yilmaz, B. and Kadioglu, Y. (2010) Development and Validation of HPLC Method for Determination of Human Insulin in Pharmaceutical Preparation. International Journal of Pharmaceutical Sciences Review and Research, 2, 40.
[10] Mosmann, T. (1983) Rapid Colorimetric Assay for Cellular and Survival: Application to Proliferation and Citotoxicity Assays. Journal of Immunological Methods, 65, 55-63.
[11] Wu, Y., Yang, W., Wang, C., Hu, J. and Fu, S. (2005) Chitosan Nanoparticles as a Novel Delivery System for Ammonium Glycyrrhizinate. Pharmaceutical Nanotechnology, 295, 235-245.
[12] Gierszewska-Druzznska, M. and Ostrowska-Czubenko, J. (2010) The Effect of Ionic Crosslinking on Thermal Properties of Hidrogel Chitosan Membranes. Progress on Chemistry and Application of Chitin and Its Derivatives, 15, 25-32.
[13] Pieróg, M., Gierszewska-Druzznska, M. and Ostrowska-Czubenko, J. (2009) Effect of Ionic Crosslinking Agents on Swelling Behavior of Chitosan Hidrogel Membranes. Progress on Chemistry and Application of Chitin and Its Derivatives, 14, 75-82.
[14] Marreco, P.R., Moreira, P.L., Genari, S.C. and Moraes, A.M. (2004) Effect of Different Sterilization Methods on the Morphology. Mechanical Properties and Cytotoxicity of Chitosan Membranes Used as Wound Dressings. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 71, 268-277.
[15] Dallan, P.R.M. (2005) Synthesis and Characterization of Chitosan Membranes for Application in Skin Regeneration. Doctorate Thesis, Universidade Estadual de Campinas, Campinas. (In Portuguese)
[16] Martins, M.T. (2007) Development and Validation of Analytical Methods, Preliminary Study of Stability and Dissolution Test to Determination of the Triazine Antiepileptic Lamotrigine in Tablets. Doctorate Thesis, Universidade Federal do Rio Grande do Sul, Faculdade de Farmácia, Porto Alegre. (In Portuguese)
[17] Watson, D.G. (2012) Pharmaceutical Analysis: A Textbook for Pharmaceutical Chemists. Churchill Livingstone, London.
[18] Bispo, V.M. (2009) Biocompatibility of Nanostructural Chitosan/Poy(Vinyl Alcohol) Blends Chemically Crosslinked with Genipin for Biomedical Applications. Thesis, Federal University of Minas Gerais, Minas Gerais.
[19] Daguano, J.K.M.F., Santos, C. and Rogero, S.D. (2007) Cytotoxicity Analysis of Bioceramics for Use in Systems of Implantations. Revista Matéria, 12, 134-139. (In Portuguese)

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