Design, synthesis and characterization of dendritic macromolecules and their potential applications in drug delivery.

摘要

Dendritic macromolecules have highly branched three-dimensional features that mimic the structure of trees. This new kind of polymeric materials has attracted much attention in recent years due to their unique globular structure, chemical reactivity, and properties. In general, dendritic macromolecules include several different types of structures, dendrimers with perfect structures, hyperbranched polymers with irregular structures, and dendritic hybrids incorporating both linear and globular macromolecular fragments. Described in this thesis are several different studies on the synthesis and characterization of new dendritic systems, and the preliminary exploration of their potential applications as novel drug delivery agents.; Chapters 2, 3 and 4 describe the design and synthesis of new dendritic systems for drug delivery applications. Chapter 2 describes the simple design of a dendritic system for drug delivery that makes use of the well-controlled surface chemistry characteristic of dendrimers. A new dendrimer with two types of surface functionalities, which can be addressed chemoselectively, was designed and synthesized. One type of functionality is targeted for attachment of solubilizing groups to afford water solubility to the entire molecule, while the other functionality is reserved for the attachment of hydrophobic model drugs. In chapter 3, the direct attachment of model "drugs", folic acid and methotrexate, onto hydrazide-terminated dendrimers was investigated. Chapter 4 deals with the potential use of dendritic micelles as novel drug delivery agents. A new type of dendritic unimolecular micelles was designed and prepared, and these micelles were shown to be capable of entrapping the model drug indomethacin with subsequent sustained release.; Chapters 5 and 6 describe earlier work on the surface modification of poly(propylene imine) dendrimers. Starting from poly(propylene imine) dendrimers, different side chains were attached to the amino surface groups of the dendrimers through simple coupling reactions, affording a variety of dendritic materials. These dendritic macromolecules may be useful as rheology control agents, lubricants, and fuel additives.; Finally, chapter 7 describes a new approach to hyperbranched polyesters by ring-opening polymerization of an AB-type monomer. The degree of branching of the resulting hyperbranched polyesters was determined from 13C-NMR. The new hyperbranched polymers may be useful in the design of new bioerodible materials.