Study On Cyclodextrin Based Supramolecular Polymer Micelles

Polymer materials based on renewable resources and spramolecular assemblies have attracted much attention in recent years. Due to the excellent biocompatibility and biodegradability, poly(s-caprolactone)(PCL), cyclodextrin (CD) and cellulose have been found various applications in biomedical materials, controlled drug delivery systems, pharmaceutics, and so on. Supramolecular assemblies constructed by cyclodextrin inclusion complexes have drawn more attentions of the researchers from various fields owing to their unique properties. In this thesis, PCL and cellulose derivatives were used as guest molecules to construct new supramolecular polymer micelle systems driven by the host-guest interactions between cyclodextrin and the polymer.In chapter1, the latest research progress and applications of PCL and cellulose were introduced, and the development of supramolecular assemblies based on cyclodextrin pseudopolyrotaxane was reviewed.In chapter2, the design and preparation of supramolecular polymer micelles, which are self-assembled from a-cyclodextrin-threaded supramolecular pseudo-tri-block polymer (PCL-?-CD/Ad-PCL-Ad/?-CD-PCL) are described. The resulting tri-block polymer which consists of a middle block of PCL and two flanking blocks of multiple a-CD rings threaded on the PCL can self assemble to form a core-shell structure in aqueous medium, which is directed by inclusion interaction between adamantyl units and ?-CD. The hydrophobic PCL-Ad parts serve as the core of assemblies, while the pseudopolyrotaxane (a-CD/PCL-P-CD) act as the outer shell. The structure and morphology of the supramolecular polymer micelles have been characterized by1H NMR spectra, FT-IR spectra, XRD, TEM, and fluorescence spectra. The self-assembled micelles were spherical morphology with average particle size of20-40nm. The critical micelle concentration (CMC), which is a measurement characterizing the physical property of the micelles that relates to micelle's stability, increases from19.95mg/L to48.98mg/L with the molecular weight of the PCL-?-CD. The drug release behavior of the supramolecular polymer micelles was evaluated using prednisone acetate as a model drug. The drug-loaded micelles showed steady and long time (930hours) drug release behavior.In chapter3, cyclodextrin carbamates were synthesized from cyclodextrin and urea by microwave-assisted method. Cyclodextrin carbamates with different degree of substitution can be prepared by controlling microwave power and reaction time. It was a facile and environmentally friendly method for the synthesis of cyclodextrin derivatives. The supramolecular polymer micelles were prepared via the self-assembly of the pseudopolyrotaxane based on cyclodextrin carbamates and cellulose derivatives. The urea modified cyclodextrin showed the higher yield than the physical mixture of urea/cyclodextrin in the micellization with cellulose derivatives. The spherical supramolecular polymer micelles with diameters ranged from20to60nm were obtained, showed low CMC (6.67mg/L for U-y-CD/CAB micelle). The sustained release of drug was observed up to500hours. These results suggest that the cyclodextrin carbamate/cellulose derivative micelles could be a candidate for long time drug release.In chapter4, ?-cyclodextrin carbamates with different degree of substitution can be prepared by controlling microwave power and reaction time. The supramolecular polymer micelles with core-shell structure were prepared via the host-guest interaction between ?-cyclodextrin carbamates and PCL, using the sections of inclusion complexes of P-cyclodextrin carbamates and PCL as hydrophilic corona and the naked polymer as hydrophobic core. The average size of micelles was examined to be20-50nm with spherical shape. For U-P-CD/PCL (DS=4) micelle, the CMC is only2.68mg/L. The drug release behavior of the supramolecular polymer micelles was evaluated using prednisone acetate as a model drug. The loaded drug was released almost linearly against time for almost500hours with certain amount of initial burst release in the first7hours.In chapter5, new supramolecular polymer micelles via the host-guest interaction between y-cyclodextrin and PCL with core-shell structure were constructed. The CMC value is47.4mg/L and23.2mg/L for y-CD/PCL micelle and Suc-?-CD/PCL micelle respectively. The average size of blank or drug loaded micelles was verified to be20-40nm with spherical shape. The drug release rate of the micelle at pH=7.4was twice than that at pH=1.2for the constant release stage. The pH-dependent drug release behavior could attribute to the effect of pH value on the hydrogen bonds between the y-cyclodextrins.In chapter6, poly(vinyl alcohol)-g-poly(?-caprolactone)(PVA-g-PCL) was synthesized by ring opening polymerization of ?-CL using PVA as initiator under microwave irradiation. Supramolecular polymer micelles with core-shell structure were obtained from PVA-g-PCL and a-CD. The loaded prednisone acetate was released almost linearly against time for almost440hours. The micelles have excellent drug release behavior, might have great potential as drug delivery carrier with controlled release behavior.