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Thermosensitive Microparticles Based on Unsaturated Esters of some Poly- and Oligosaccharides: Preparation,Characterization, Drug Inclusion and Release
Authors:Mihaela Hamcerencu  Marcel Popa  Jacques Desbrieres  Gerard Riess
Institution:1. Technical University “Gh. Asachi”, Faculty of Industrial Chemistry and Protection of the Environment, Department of Natural and Synthetic Polymers,71 A, Bd. D. Mangeron, 700050 Iasi, Romania

Université de Pau et des Pays de l′Adour - IPREM/EPCP (UMR CNRS 5254) - Hélioparc Pau Pyrénées - 2 Avenue P. Angot - 64053 PAU cedex 09 - France

Université de Haute Alsace - Ecole Nationale Supérieure de Chimie - Equipe de Chimie Macromoléculaire, Laboratoire de Chimie Organique,Bioorganique et Macromoléculaire - 3, rue Alfred Werner, 68093 MULHOUSE Cedex, France;2. Technical University “Gh. Asachi”, Faculty of Industrial Chemistry and Protection of the Environment, Department of Natural and Synthetic Polymers,71 A, Bd. D. Mangeron, 700050 Iasi, Romania;3. Université de Pau et des Pays de l′Adour - IPREM/EPCP (UMR CNRS 5254) - Hélioparc Pau Pyrénées - 2 Avenue P. Angot - 64053 PAU cedex 09 - France;4. Université de Haute Alsace - Ecole Nationale Supérieure de Chimie - Equipe de Chimie Macromoléculaire, Laboratoire de Chimie Organique,Bioorganique et Macromoléculaire - 3, rue Alfred Werner, 68093 MULHOUSE Cedex, France

Abstract:Summary: The paper concerns the preparation and characterization of hydrogel microparticles based on exopolysaccharide (Gellan, Xanthan) unsaturated derivatives and respectively on cyclodextrin as well as their application for some hydrosoluble and liposoluble drugs inclusion. In the first step the polysaccharide and cyclodextrin unsaturated esters (maleate, acrylate) were synthesized and their hydrogel forming capacity was tested using a grafting-crosslinking free-radical reaction with N-isopropyl acrylamide (NIPAm), at room temperature. For a better control of the crosslinking degree N,N' methylene-bis-acrylamide (BIS), replaced by cyclodextrin tri-acrylate (A-CD) in a few experiments, was used. The microparticles were obtained by using the method in w/o emulsion, in which the dispersed aqueous phase is the reaction mixture and the oil phase is hexane. The particles containing polysaccharide esters showed an average diameter around 100 µm when crosslinking was achieved with BIS. They were smaller than those crosslinked with A-CD, which are in the range of 200-300 µm; the particles based on Xanthan maleate were smaller than Gellan maleate based ones. Even much smaller particles (2-2.5 µm in diameter) were obtained by starting from A-CD grafted-crosslinked systems. The synthesized microparticles are able to include chloramphenicol, as well as progesterone; the drug is slowly released according to diffusion controlled kinetics. The application of these microparticles in emergency ophthalmic treatments is possible as a result of their thermal sensitivity; they can collapse and release the drug instantly when placed in contact with the human eye, at 37 °C.
Keywords:cyclodextrin  drug release  microparticles  polysaccharide  thermosensitive hydrogel
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