SCAN:Thermoresponsive Hydrogels as Drug Delivery Systems

Abstract

Controlled release from biocompatible materials has received recently much attention for its biomedical applications. Due to their biocompatibility and biodegradability, gluocopyranosides such as chitosan and dextran appears as promising polymer materials if one is able to regulate their rheological properties and the encapsulation/release efficiency. In this work we prepared graft polymer gel particles from chitosan (“medium” Mw) and dextran (Mw=5-40x10⁶). The starting polymers were dissolved in the approprite aqueous media (simple water for dextran, and 5% acetic acid for chitosan) in the suitable semi-dilute concentration range (1-4% w/v) and as graft polymer we used N-isopropylacrylamide (NIPAAm). The reaction was initiated either using gama radiation or ammoniumcerium (IV)–nitrate radical initiator and as far as the gel rheology gama radiation gives more consistent gel particles. FT-IR data for the grafted Dex-NIPAAm systems revealed the presence of two peaks around ~1650 and ~1550 cm-1 which can be ascertained with the typical amide I and II bands of NIPAAm, revealing the success of the grafting reaction; this was also confirmed by 1H-NMR. As model drug we used a potent antiemetic substance used in the prevention of chemotherapy-induced nausea and vomiting, ondansetron, (±) 1, 2, 3, 9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-4H-carbazol-4-one (hydrochloride form) which was incorporated in the gel particles both before and after the co-polymerization. Swelling capacity and cycles of incorporation/release of the drug were evaluated with essays where PBS solution’s pH and temperature were varied in the physiological range of interest (withdrawing of aliquots and HPLC analysis). Results showed that, irrespective of the polymers, there is a positive correlation between co-polymer concentration and swelling, as well as with drug incorporation. Release essays show an initial burst followed by slow release but no significant pH dependence (in the range of interest) and a moderate dependence with temperature.
 

Short CV

1999-2003 – Degree in Chemical Engineering by Ciences and Technology Faculty of University of Coimbra

July till December 2003 – Research fellowship under the Prodep III program in biomaterials in partnership between University of Coimbra and IBET.

January till October 2004 – Research fellowship under PRAI program in cellulose materials in the University of Coimbra.

Since October 2004 – PhD fellowship in Chemical Engineering supervised by Prof. Maria Helena Gil from University of Coimbra, and Prof. António Lopes from ITQB.