It is well recognized that physical and chemical properties of materials can alter dramatically at nanoscopic scale, and the growing use of nanotechnologies requires careful assessment of unexpected toxicities and biological interactions. However, most in vivo toxicity concerns focus primarily on pulmonary, oral, and dermal exposure to ultrafine particles. As nanomaterials expand as therapeutics and as diagnostic tools, parenteral administration of engineered nanomaterials should also be recognized as a critical aspect for toxicity consideration. Due to the complex nature of nanomaterials, conflicting studies have led to different views of their safety. Here, the physicochemical properties of four representative nanomaterials (dendrimers, carbon nanotubes, quantum dots, and gold nanoparticles) as it relates to their toxicity after systemic exposure is discussed.

With very few adjuvants currently being used in marketed human vaccines, a critical need exists for novel immunopotentiators and delivery vehicles capable of eliciting humoral, cellular and mucosal immunity. Such crucial vaccine components could facilitate the development of novel vaccines for viral and parasitic infections, such as hepatitis, HIV, malaria, cancer, etc. In this review, we discuss clinical trial results for various vaccine adjuvants and delivery vehicles being developed that are approximately nanoscale (<1000 nm) in size. Humoral immune responses have been observed for most adjuvants and delivery platforms while only viral vectors, ISCOMs and Montanide ISA 51 and 720 have shown cytotoxic T cell responses in the clinic. MF59 and MPL have elicited Th1 responses, and virus-like particles, non-degradable nanoparticles and liposomes have also generated cellular immunity. Such vaccine components have also been evaluated for alternative routes of administration with clinical successes reported for intranasal delivery of viral vectors and proteosomes and oral delivery of a VLP vaccine.

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Angiogenesis has long been a desired therapeutic approach to improve clinical outcomes of conditions typified by ischemia. Vascular endothelial growth factor (VEGF) has demonstrated the ability to generate new blood vessels in vivo, but trials using intravenous delivery have not yet produced clinical success. Localized, sustained delivery of VEGF has been proven necessary to generate blood vessels as demonstrated by implantable, controlled release devices. Ultimately, nanoparticles delivered by intravenous injection may be designed to accumulate in target tissues and sustain the local VEGF concentration; however, injectable nanosuspensions that control the release of stabilized VEGF must first be developed. In this study, we utilize the heparin binding domain of VEGF to bind the polyanion dextran sulfate, resulting in an enhanced thermal stability of VEGF. Coacervation of the VEGF-bound dextran sulfate with selected polycations (chitosan, polyethylenimine, or poly-L-lysine) produced nanoparticles approximately 250 nm in diameter with high VEGF encapsulation efficiency (50-85%). Release of VEGF from these formulations persisted for >10 days and maintained high VEGF activity as determined by ELISA and a mitogenic bioassay. Chitosan-dextran sulfate complexes were preferred because of their biodegradability, desirable particle size ( approximately 250 nm), entrapment efficiency ( approximately 85%), controlled release (near linear for 10 days), and mitogenic activity.