DENVER – As the nanotechnology field evolves, there are at least three reasons a clinician might prefer to use nanoparticles over conventional drugs, according to Dr. Jack L. Arbiser. The first is to minimize the effects of a systemic drug.
"What if steroids could be directed to the site of the pathologic lesion but not cause side effects such as glucose intolerance, bone fractures, or gastric ulcers?" he asked during a session on nanotechnology at the annual meeting of the American Academy of Dermatology. "What if propranolol could be given to patients with hemangiomas without having to worry about cardiac side effects?"
A second reason to turn to nanoparticles would be to use highly toxic substances in a safe way, continued Dr. Arbiser, a professor of dermatology at Emory University, Atlanta. "We already use Botox by injection, which is one of the most toxic substances known to man, but what if other highly toxic substances could be specifically delivered to cancers, infections, or inflammation?"
A third reason to use nanoparticles is that they may offer a way for compounds "that are not highly active be delivered to sites of disease in high enough concentration so that they have therapeutic activity and provide a high measure of safety," he said.
Dr. Arbiser discussed his nanotechnology experience as part of a research team developing a derivative of gentian violet for cancer treatment. He and his associates observed that gentian violet has potential antitumor activity through inhibition of NADPH (nicotinamide adenine dinucleotide phosphate) oxidase. However, the researchers faced early challenges, because gentian violet is not patentable by itself, and, because it is hydrophilic, it may not pass through the blood-brain barrier.
"Our solution was to synthesize and patent a more lipophilic derivative of gentian violet called imipramine blue," Dr. Arbiser explained. "We packaged it in liposomes so it has a much longer half-life and is directed to tumors because liposomes preferentially localize to leaky blood vessels."
Imipramine blue can be given weekly and is efficacious against cancer tumors. Dr. Arbiser and his associates have demonstrated that systemic delivery of imipramine blue significantly inhibited migration of glioblastoma cells into the brain parenchyma (Sci. Transl. Med. 2012;4:127ra36).
"We also see this [inhibition of spread] in prostate, breast, and melanoma cells," he said. "So it seems to be hitting the same pathway in multiple different tumor types." Such an approach targets delivery of therapeutic and diagnostic imaging agents to the site of cancer and chronic inflammation/infection, potentially reducing side effects and increasing efficacy.
"My own personal bias is that we should start using metal-based nanotechnology for severe illnesses, such as cancers, allowing the effects of these materials to be studied in humans, before widespread introduction into cosmetics," he concluded.
Dr. Arbiser disclosed that he is the cofounder of companies ABBY Therapeutics and Accuitis.