Approaches for the preparation of non-linear amphiphilic polymers and their applications to drug delivery

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Abstract

Amphiphilic polymers are particularly useful for drug delivery because of their ability to self-assemble into discrete aggregates. While this behavior has been studied in depth for simple linear block copolymer amphiphiles, recent advances in synthetic methodologies have provided efficient routes to amphiphilic polymers with more complex architecture, including dendrimers, hyperbranched polymers, star polymers, and cyclic polymers. These architectures can impart unique advantages, such as increased stability, on their micellar aggregates. Herein the different strategies for preparing these complex amphiphiles are described, and the application of their assemblies towards drug delivery are summarized.

Introduction

Amphiphilic polymers are a useful subset of macromolecules, which exhibit both hydrophobic and hydrophilic regions within their covalently bound structure. Their synthesis and applications have received increased attention recently due to their broad utility. Because of the differing solubilities of their contrasting regions, amphiphilic polymers exhibit an inherent ability to self-assemble in their solution phase when one block exhibits poor compatibility with the solvent. By tuning the size and shape of amphiphilic polymers, a variety of morphologies can be accessed via self-assembly, including spherical, rod-like, lamellar, and vesicular assemblies. The ability to self-assemble into complex structures makes these materials attractive candidates as hosts in a range of applications, including drug delivery, catalysis, imaging, and sensing.

The majority of the research on amphiphilic polymers has involved simple linear block copolymers, and much of this work has been reviewed in detail elsewhere [1], [2], [3], [4], [5], [6]. In contrast, this review seeks to provide an overview of the limited, but growing, research on amphiphilic polymers with more complex, non-linear architectures. This review will be organized by the following architectural classes of polymers: amphiphilic dendrimers, hyperbranched polymers, star polymers, and cyclic polymers.

Section snippets

Amphiphilic dendrimers

Dendrimers are highly branched macromolecules that exhibit regular branching and structural symmetry. These monodisperse, globular macromolecules bear a multiplicity of terminal groups near the surface and therefore exhibit high surface functionality and reactivity. Their dense, compact dendritic structure results in reduced chain entanglement and a smaller hydrodynamic radius relative to linear polymer analogs of identical molecular weight. Amphiphilic dendrimers, in addition to their

Amphiphilic hyperbranched polymers

In response to the tedious synthesis of true dendrimers, hyperbranched polymers have attracted more interest as a branched polymeric scaffold. Hyperbranched polymers can be prepared in one step, affording the condensed, multifunctional structure of dendrimers but exhibiting a much less perfect structure, a broader distribution of molecular weights, and a less defined degree of branching [51]. Research on hyperbranched polymers has grown rapidly since the earliest theoretical work by Flory in

Star polymers

Star polymers have also been explored as an alternative polymer architecture because they exhibit similar properties to dendrimers (e.g. globular structure, multiple end groups, reduced viscosity) but feature accelerated and tunable methods of synthesis. Star polymers, which consist of multiple arms attached to a central core, were first reported by living anionic polymerization in the 1950s and have been the subject of extensive research since then. Amphiphilic star polymers, which incorporate

Cyclic polymers

Cyclic polymers exhibit a number of interesting properties, including reduced viscosity and glass transition temperatures, owing to their lack of end groups and their confined conformational freedom. [103] Cyclic polymers have potential for biomedical applications because their cyclic conformation has been demonstrated to result in increased blood circulation times [104] and improved targeting to tumor tissue via the enhanced permeability and retention effect. [105] In addition, degradable

Conclusions

The importance of covalent architecture for polymeric drug delivery systems is a topic that has only recently been investigated in detail. The recent growth of this research field has been bolstered by the development of improved synthetic methodologies. For example, living radical polymerization not only provides access to diverse side chain functionalities but also enables efficient functionalization of polymer end groups. Likewise, improved methodologies for incorporating branching and

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    This review is part of the Advanced Drug Delivery Reviews theme issue on “Approaches to drug delivery based on the principles of supramolecular chemistry”.

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