Organic nanoparticles for drug delivery and imaging
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Introduction Organic nanoparticles prepared from various materials, including polymers and lipids, have found exciting applications in therapeutic delivery and imaging (Figure 1).1 Nanoparticles offer distinct advantages over free drugs, including encapsulation, sustained or triggered release, and targeting to diseased sites. Encapsulation avoids exposure of drugs to off-target tissues. This provides a particular advantage for toxic drugs such as chemotherapeutics, where off-target toxicity is a key hurdle. Controlled release kinetics is also a key issue in drug delivery since pharmacokinetics often has a direct influence on therapeutic efficacy and toxicity. By choosing appropriate materials and design features, drugs can be delivered in a sustained or triggered manner. The ability of nanoparticles to target diseased tissues is perhaps their most appealing feature. Targeting has the potential to reduce off-target effects and enhance accumulation at the diseased site. To date, tens of thousands of publications have reported various aspects of nanoparticle-mediated drug delivery. These include reports on novel materials and nanoparticle design, new applications of nanoparticles, and a better understanding of fundamental hurdles that limit the utility of nanoparticles. Advances in nanoparticle design and understanding have also led to new products, although the rate of conversion of scientific advances into commercial products has been alarmingly low. While only a handful of nanoparticle therapies are
commercially available, a large number are in the pipeline at various stages of development. This issue of MRS Bulletin is focused on some of the important recent advances in the use of organic nanoparticles for drug delivery and imaging.
Design consideration for nanoparticles The design of nanoparticles, characterized by their material composition, size, shape, flexibility, and surface properties, essentially dictates their therapeutic outcome. A variety of materials have been used to synthesize nanoparticles, although lipids and polymers continue to be among the leading choices. Various synthetic polymers, including poly(lactic-co-glycolic) acid (PLGA), polyanhydrides, and dextrans, as well as natural polymers, including elastin-like polypeptides, have been used for preparing nanoparticles.2,3 The utility of these materials is determined by their toxicity, manufacturability, and compatibility with the drug. Hydrophobic drugs, which include many chemotherapeutic agents, can be easily encapsulated in hydrophobic polymers such as PLGA, whereas encapsulation of peptides and proteins in nanoparticles requires stringent considerations due to their susceptibility for unfolding, denaturation, and degradation. Polymer particles of various sizes from a few tens of nanometers to several micrometers have been synthesized and used for drug delivery. Many methods of nanoparticle synthesis have also been scaled-up: emulsification and
Samir Mitragotri, University of California, Santa Barbara; [email protected] Patrick Stayton,
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