Cyclodextrin-Based Biodegradable Polymer Stars: SYNTHESIS, Degradation and Fluorescence Studies

In controlled release, each patient's body displays different pharmacokinetics for the degradation of the drug delivery system affecting the release of the bioactive compound. The proposed research aims to develop polymeric systems based on a host/guest core capable of indicating controlled release by fluorescence. Specifically, this involves the development of a prototype material based on a cyclodextrin molecule that serves as a framework for biodegradable polymer arms.;Polymer stars were synthesized based on core- and arm-first methods. For core-first synthesis, stars based on a heptakis(2,6-di-O-methyl)-beta-cyclodextrin core that supports 7 polymer arms of poly(lactic acid) (PLA), poly(3-hydroxybutyrate) (PHB) or poly(lactic-co-glycolic acid) (PLGA) were synthesized by ring-opening polymerization with variation in both the polymer microstructure and arm length. Use of Sn(Oct)2 as a catalyst yielded polymers with high PDI values and poor molecular weight correlation. Switching to the A1[salen] system yielded polymers with excellent PDI values but low molecular weight correlation.;For arm-first synthesis, copper-catalyzed azide-alkyne cycloaddition was used to synthesize 7 arm stars based on a beta-CD-(N3) 7 and acetylene terminated polymers of PLA, PHB, PCL and PLGA. Excellent levels of control and good molecular weight correlation was obtained from arm-first synthesis. However, isolation of these stars was challenging, resulting in low yields.;Analysis of these polymers by 1H NMR spectroscopy revealed the polymer composition whilst differential scanning calorimetry gave glass, melt and crystallization temperatures. Decomposition temperatures were also investigated by thermogravimetric analysis. Molecular weights and polydispersities of these polymers were determined by using gel permeation chromatography coupled with light scattering detectors as well as 1H NMR spectroscopy.;Binding constant and correlation studies were successfully conducted with beta-cyclodextrin and heptakis(2,6-di-O-methyl)-beta-cyclodextrin with 7-methoxycoumarin using solvent systems of water and methanol and pure water. Studies on beta-CD in H2O gave a binding constant of 238 M-1 and an R2 value of 0.9580. Stronger binding and a better correlation was obtained with heptakis(2,6-di-O-methyl)-beta-CD in H2O with a binding constant of 306 M-1 and R 2 value of 0.998. Binding in H2O/MeOH was also tested with heptakis(2,6-di-O-methyl)-beta-CD resulting in a weaker binding constant of 120 M-1 and lower correlation value of 0.986 due to the decrease in solution polarity.;A 7-methoxycoumarin fluorophore was used to demonstrate the controlled release characteristics of these novel materials by fluorescence spectroscopy by uncatalyzed and enzyme catalyzed degradations, showing that they have potential as controlled release vectors.