NANOMEDICINE AND NANOBIOTECH

Editor’s Note: Listed are selected abstracts from recent issues of Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology, which is published by John Wiley & Sons, which also publishes Pharmaceutical Formulation & Quality. For more on these studies and others, go to http://wires.wiley.com/nanomed.

Scanning electron microscopy image of dexamethasone acetate-loaded (D,L-lactide-co-glycolide) nanoparticles (scale bar 1 µm).

Review: Toxicity of Nanomaterials to the Eye

What do nanoparticles offer drug delivery to the eye that traditional formulations do not? The underlying concept of nanomedicine is that the nanomaterials have properties that their constituent components do not have. These unique properties are the benefit, but the cost can be more a complicated toxicology assessment.

Ocular delivery of therapeutic nanoparticles has the potential to greatly increase the quality of life through maintaining our vision. The eye is composed of multiple tissue types, i.e., epithelium, muscle, immune cells, neural cells, and blood vessels, to name a few. Ocular diseases affect many of these tissues at once. Introducing novel therapeutic nanoparticles and determining mechanisms of toxicity becomes challenging.

This review is a survey of what is known about toxicity in experimental nanoparticles for ocular therapeutics. Specific cases are chosen to illustrate a range of toxic effects of nanoparticles in the eye. There is a unique research opportunity for in-depth toxicology studies of nanoparticles in the eye. This has been made possible by the rapid development of therapeutic nanoparticles in the last few years.

Prow TW. Toxicity of nanomaterials to the eye. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology. 2009; Volume 1, Issue 4:317-333. Correspondence to Tarl W. Prow, Therapeutics Research Unit, University of Queensland at t.prow@uq.edu.au.

---

The core-shell architecture of a poly(amidoamine) (PAMAM) dendrimer with an ethylene diamine core with a typical generation numbering scheme. Half-generation PAMAM dendrimers may have carboxyl or methyl ester terminal groups. Unmodified full-generation PAMAM dendrimers have amine surface groups.

Review: Toxicity and Requirements for Development of Dendrimer-Based Pharmaceuticals

Dendrimer conjugates for pharmaceutical development are capable of enhancing the local delivery of cytotoxic drugs. The ability to conjugate different targeting ligands to the dendrimer allows for the cytotoxic drug to be focused at the intended target cell while minimizing collateral damage in normal cells.

Dendrimers offer several advantages over other polymer conjugates by creating a better defined, more monodisperse therapeutic scaffold. Toxicity from the dendrimer, targeted and nonspecific, is not only dependent upon the number of targeting and therapeutic ligands conjugated, but can be influenced by the repeating building blocks that grow the dendrimer, the dendrimer generation, as well as the surface termination.

McNemy DQ, Leroueil PR, Baker JR. Understanding specific and nonspecific toxicities: a requirement for the development of dendrimer-based pharmaceuticals. Wiley Interdisciplinary Reviews: Nanomedicine and Nanotechnology. 2010; Volume 2, Issue 2: 249-259. Correspondence to Daniel Q. McNemy, Department of Chemical Engineering, Michigan Nanotechnology Institute for Medicine and Biological Sciences at dmcnemy@umich.com.

---

Schematic of neo-proteoglycan. The multiwalled carbon nanotubes are coated with poly(ethyleneimmine), where CNBr-activated heparin can interact with the exposed amine groups.

Review: Heparin-Based Nanoparticles

The combination of nanoparticles and biological molecules is of intense interest because of the synergistic properties offered by such newly synthesized composites. Heparin (HP), conjugated to nanomaterials, has recently been investigated for its chemical and biological properties. HP has a number of biological activities that can be enhanced when composited with nanoparticles. In addition, HP improves the biocompatibility of nanoparticles improving their performance in various biological applications.

A variety of recent research combines HP and nanomaterials for a myriad of applications. HP has been conjugated to the surface of the nanoparticles, such as magnetic and metallic nanoparticles, or biodegradable and nondegradable synthetic polymers. HP has also been incorporated into the nanoparticles. There are numerous possibilities for material composites and chemistries that incorporate HP. This opens the door for novel applications ranging from improving anticoagulant activity, for anticancer and antitumor therapy, to tissue engineering and biosensors. This review examines the different possibilities of HP-based nanoparticle composites and their medicinal or biological applications.