Biomedical Engineering Reference
In-Depth Information
4
Cytotoxicity of Stimuli-
Responsive Nanomaterials
Predicting Clinical Viability through
Robust Biocompatibility Profiles
Daniel Wehrung and Moses O. Oyewumi
CONTENTS
4.1 Introduction .......................................................................................................................... 103
4.2 Photoresponsive Materials .................................................................................................... 104
4.3 pH-Responsive Systems ........................................................................................................ 106
4.4 Enzyme-Responsive Systems ............................................................................................... 107
4.5 Factors Influencing Biocompatibility of Stimuli-Responsive Nanomaterials ...................... 107
4.6 Representative Methods of Biocompatibility Assessment for Stimuli-Responsive
Nanomaterials ....................................................................................................................... 108
4.7 Perspectives on the Field of Stimuli-Responsive Biomaterials ............................................ 109
Acknowledgments .......................................................................................................................... 112
Abbreviations ................................................................................................................................. 112
References ...................................................................................................................................... 113
4.1 INTRODUCTION
Recent advances in synthetic methods of polymerization such as controlled-radical polymeriza-
tion, encompassing atom transfer radical polymerization, reversible addition-fragmentation chain
transfer, and nitroxide-mediated polymerization have allowed more control over polymerization
reactions and as such, allowed the development of increasingly sophisticated polymers (Sauer et al.,
2001; Checcot et al., 2003; Rakhmatullina et al., 2007). These and other advancements in synthetic
techniques have facilitated the development of stimuli-responsive or “smart” drug delivery systems.
Stimuli-responsive delivery systems respond to some form of stimuli, be it external or internal.
External stimuli are those that are applied from outside the body and include light, magnetic fields,
and ultrasound; while internal (also known as proximal) stimuli are those found in the microen-
vironment of a specific part of the body (e.g., diseased tissue) or a specific cellular compartment
(e.g., lysosome). Internal stimuli include pH, redox potential, local temperature, and enzyme over-
expression. Regardless of the form of stimuli used to activate the system, the overarching principle
remains the same; when the material is activated by its stimulus, it undergoes a physical/chemical
change (hydrophobic-hydrophilic balance, oxidation state, secondary structure), which results in
the release of entrapped therapeutic payloads. This allows for temporal and spatial control of drug
release from the system, which in turn increases drug efficacy, decreases side effects, and enhances
the therapeutic window.
The potential benefits that these systems offer have not gone unnoticed, and there has been a
rapid increase in the number of publications centered on stimuli-responsive drug delivery systems
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