Environmentally responsive materials based on block-, graft-, and cross-linked copolymers for pharmaceutical applications.

摘要

Polymer materials have been developed for various biomedical applications. This thesis document attempts to develop and characterize novel classes of environmentally responsive polymer complex materials for drug delivery. These materials are based on block-, graft-, and cross-linked copolymers that contain the following major elements of different functionality: (1) hydrophilic ("water-soluble") polymer block, polyethylene oxide (PEO); (2) hydrophobic ("water-insoluble") block, polypropylene oxide (PPO); (3) anionic polyelectrolyte block, polyacrylic acid (PAA). The hydrophilic PEO block facilitates dispersion or swelling of the materials in an aqueous environment. The hydrophobic PPO block exhibits temperature dependent hydration/dehydration behavior that was employed to prepare the temperature responsive materials. The polyelectrolyte PAA block can bind oppositely charged molecules such as salts, surfactants, and proteins and serves as a structural domain that is responsive to changes in pH and ionic strength.;Three basic types of materials were studied: (1) blends of PEO-PPO-PEO block copolymers (PluronicRTM) of different block length, (2) complexes of PAA grafted with PluronicRTM (Pluronic-PAA) and cationic surfactants, (3) cross-linked networks of PEO and PAA (PEO- cl-PAA) with proteins. First, mixtures of hydrophilic and hydrophobic PluronicRTM displayed a temperature dependent self assembly behavior, forming micellar aggregates of different structures. The aggregates were characterized with small size (100 nm to 250 nm), high stability in dispersion, and greater solubilization capacity with respect to hydrophobic compounds compared to micelles formed by one type of PluronicRTM. Second, stable dispersed block ionomer complexes (BIC) were formed by mixing Pluronic-PAA and cationic surfactants. These complexes exhibited a thermotropic and pH sensitive behaviors, displayed high solubilization capacity with respect to hydrophobic drugs that incorporated into domains formed by surfactant tails bound to the PAA chains. Third, the polyelectrolyte networks of PEO- cl-PAA showed the pH and salt dependent swelling, and displayed high capacity for sorption of a protein, cytochrome C, due to formation of electrostatic complex between polyelectrolyte and protein. By adding Ca2+, the protein was released from the complex in the external medium. Overall this study developed three new classes of functional nanoscale materials for future applications in the controlled drug release and delivery systems.