Formation and characterization of novel cyclodextrin containing polymeric inclusion complexes and their application

• Main Author: Truong Le Bich Tram
• Other Authors: Po-Da Hong
• Format: Others
• Language: en_US
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/09377610450127597510

博士 === 國立臺灣科技大學 === 應用科技研究所 === 101 === Structures with well-defined architectures and tailored physical properties can be produced by supramolecular self-assembly of polymeric inclusion complexes (ICs) consisting of cyclodextrins (CDs). Recently, there has been significant interest in the use of polymers to design novel supramolecular nanostructures as these polymers micelles and hydrogels under inclusion complexation. Cyclodextrins have the ability to spontaneously form complex structures with guest molecules. The complexation of polymers with CD induces self-assembed polymers which can be useful in various fields. This dissertation mainly focuses on the formation, characterization and application of some novel cyclodextrin inclusion complex-containing biodegradable polymeric systems. The dissertation begins with a detailed introduction followed by a description of the experiments in the second chapter. The third chapter of the dissertation covers the synthesis of a new drug carrier obtained by using folic acid (FA) covalently incorporated into a supramolecular hydrogel network. For this attempt, FA was first conjugated with α-CD to form α-CD-FA and then used to interact with Poly(ethylene glycol) methyl ether (MPEG) in an aqueous solution. The formation of the supramolecular hydrogel, its gelation kinetics, mechanical strength, shear-thinning behavior and thixotropic response were investigated using nuclear magnetic resonance (1H NMR), wide angle X-ray diffraction (WAXD), Fourier-transform infrared (FT-IR) and rheological measurements with respect to the effects of MPEG and α-CD-FA amounts. Meanwhile, the possibility of using this hydrogel matrix for an injectable drug delivery system was also explored. From in vitro release and cell viability tests, it was found that the resultant hydrogel material has a great potential to act as an injectable matrix for the encapsulation and sustained release of the modelled drug, doxorubicin hydrochloride (Dox). The fourth chapter of the dissertation explains the α-CD induced micellization of poly (ε-caprolactone-block-4-vinylpyridine) (PCL-b-P4VP) using selective inclusion of the α-CD rings onto a segment of PCL-b-P4VP by the formation of pseudopolyrotaxane-b-P4VP. The formation of micelle in aqueous media was studied. The supramolecular structure of the nano-sized micelles was demonstrated by using transmission electron microscopy (TEM), atomic force microscopy (AFM) and dynamic light scattering (DLS). It was found that pseudopolyrotaxane-b-P4VP can form into self-assembled core-shell micelles. The resultant complex micelles consist of PCL/α-CD ICs core with P4VP chains as the shell, and they have a well-defined spherical morphology. The number of P4VP segments to PCL segments in PCL-b-P4VP can influence the structure of the resultant complex micelles. The arrangement of pseudopolyrotaxane-b-P4VP in ‘‘channel-type’’ crystallites derived from supramolecular columns is confirmed from the WAXD patterns. The pseudopolyrotaxane-b-P4VP based micelles were studied by cell viability testing, and the results revealed that both of them showed excellent cytocompatibility. Dox was successfully loaded into the micelles with a loading content of 14.4% and loading efficiency of 28.9% by using UV-Vis spectroscopy (UV). The Dox loaded micelles showed lower cytotoxicity than free drugs, and could efficiently deliver and release the drug into human hepatocellular carcinoma (Hep-G2) cells as confirmed by confocal laser scanning microscopy (CLSM). These properties make the polymer micelles attractive as drug carriers for pharmaceutical applications. The last chapter of the dissertation includes the polymorphic crystallization behavior of poly (1,4-butylene adipate) (PBA) in the presence of nucleation agents such as the α-CD IC with PBA (PBAIC) and IC of the poly(ε-caprolactone) (PCLIC). The formation of PBAIC and PCLIC were characterized and confirmed using 1H NMR, FT-IR and WAXD. The differential scanning calorimetry (DSC) and WAXD results suggested that some of the PBA segments remained outside the α-CD cavity even after forming IC with α-CD. WAXD investigation also confirmed that the ICs adopted a channel structure. The obtained ICs were found to exhibit nucleation effects on the crystallization and polymorphic behavior of PBA as shown by DSC and polarized optical microscopy (POM). The pure PBA shows a polymorphic crystallization behavior based on the rate of cooling from the melting state. When the cooling rate is decreased, the crystal structures change from the β-form to the α-form and vice versa. The PBA blended with nucleating agents show higher crystallization temperatures than pure PBA. Nucleating agents preferably initiate the nucleation of the α-form crystal of PBA, which is thermodynamically more stable than that of the β-form crystal of PBA. The nucleating activity of the PCLIC during the crystallization of the PBA is higher than that of PBAIC.