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Fundamental Theme 6 - Polysaccharides in human technologies
Theme leader: Carmen G. Boeriu (University of Wageningen, The Netherlands)
Abstract:
Bio-compatible (non-immunogenic) polysaccharide-based nano-carriers for drug delivery systems. This project aims at the development of new concepts for polysaccharide-based nano-carriers for target delivery and controlled release of bioactive compounds and drugs. The project focuses on the development of polymeric architectures, namely carbohydrate-based dendritic structures and cross-linked hyaluronans and in the investigation of their potential application in pharmaceutical and biomedical fields. For this, the encapsulation and the transport of guest molecules into these new nanostructures will be investigated. The structure of these nanocarriers in the unloaded and fully loaded states as well as the transport capacities will be determined. The kinetics and the mechanism of binding and of the release of bioactive compounds as well as the bioavailability of the released component will be studied. This research, when successful, will significantly improve the control over the administration of therapeutic proteins and other pharmaceutical agents.
Objectives:
a) The relation between biomedical properties and structural features of selected polysaccharides will be including the characterization and modelling aspects of polysaccharide assemblies.
b) Reassembly of the selected and modified polysaccharide derivatives for biomedical application development
State of the art:
Polysaccharides play a key role in human health and well being. The importance of carbohydrates as major food ingredient supplying energy and essential building elements for construction of healthy tissues is well known. In recent years the role of non-digestible polysaccharides (NDPS) in food has been recognized and NDPS are now finding entrance to the market as functional food ingredients and prebiotics. A wide variety of plant polysaccharides such as soluble -glucans, arabinoxylans, fructans (inulin) and pectins have been investigated for their potential as dietary supplements or smart food additives. Nutraceuticals are becoming more and more important in food industries and many new functional roles for polysaccharides and their derivatives in health food will be developed in the near future.
Other polysaccharides are important for their role in pharmaceutical applications, such as drug carriers (starch and cellulose derivatives), gels for skin care (glucomannan from Aloe) or vaccines against pathogens (capsular polysaccharides of bacteria). Many different roles for polysaccharides in medical applications have been reported from specific cytotoxicity for tumor cells (levan) to immune enhancing properties (arabinogalactans derived from larch). Carbohydrates are known to play essential roles in cell-cell recognition and immune response. Biofilms from bacterial polysaccharides (cellulose and other are investigated for their application in medical wound dressing or hygienic products. Novel drug carriers that are biocompatible and can be used for targeted drug delivery are of interest. Smart design of the nano-carrier surface will enable development of tissue specific drug delivery systems.
Key targets are to find novel polysaccharide based applications in pharmaceutical, medical, nutraceutical or cosmetic disciplines. The polysaccharides will be selected upon structural and functional criteria and designed modification of properties will be performed.
References:
1) C.G. Boeriu, G. Oudgenoeg, W.T. J. Spekking, L.B. J. M. Berendsen, L. Vancon, H. Boumans, H. Gruppen, W. J. H. van Berkel, C. Laane, and A. G. J. Voragen - Horseradish Peroxidase-Catalyzed Cross-Linking of Feruloylated Arabinoxylans with b-Casein, J. Agric. Food Chem., 52 (21), 6633 -6639, 2004.
2) P. R. Lockman, R. J. Mumper, M. A. Khan, D. D. Allen - Nanoparticle Technology for Drug delivery Across the Blood-Brain Barrier, Drug Development and Industrial Pharmacy, 28 (2002) 1-13.
3) A. Rubinstein - Natural polysaccharides as targeting tools of drugs to the human colon, Drug development research 50 (2000) 435-439 B. Tunland and Meijer, - Comprehensive review in food science and food safety, Vol3 (2002) 78-92.
4) Z. Zhu, R. Zhuo - Crosslinked Quaternary Ammonium Cornstarch Matrix for Slow Release of Carboxylic Groups-containing Herbicides, Starch 58 (2000) 58-63.
Programme of the work:
a) Preparation of novel polysaccharide derivatives: Design and synthesis of novel polysaccharide derivatives that can be used as matrix for encapsulation and controlled release of drugs.
b) Structure characterization of the synthesised polysaccharide derivatives
c) Preparation of nanoparticles loaded with bioactive compounds; sorption and desorption kinetics; encapsulation/entrapment
d) Kinetics and mechanisms of release of bioactive substances and model drugs.
e) Application tests: Assessment of bioactivity of PS derivatives; biomedical tests; studies on release of bioactive substances; Processing of new PS derivatives