A new breakthrough in nanotechnology is offering a real wow factor for drug makers – the possibility of delivering multiple drugs at once into targeted cells.
The development, reported in the Sept. 4 issue of Nature, involves the creation of double nanoemulsions, dubbed WOW (water-in-oil-in-water), which are stable at below 100 nm in diameter. This sub-100-nanometer stability for double emulsions has never been achieved before, according to researchers.
NanoPacific Holdings (Los Angeles) obtained the exclusive rights from the California NanoSystems Institute (CNSI) at the University of California-Los Angeles (UCLA).
They are "the world's smallest double emulsions," said co-CEO and Chairman Joseph Boystak. He noted that they contain "oil- and water-based structures, so we can load them with both hydrophobic and hydrophilic materials."
NanoPacific, founded in December 2007, formed a partnership with CNSI, and currently holds three exclusive licenses from the institute – all related to nanodelivery mechanisms. CNSI is a partnership between UCLA and UC Santa Barbara, established in 2000 through a State of California initiative to combine academic research and private sector. It has been awarded up to $350 million in federal research grants, in addition to industry funding.
Timothy Deming, chairman and professor of bioengineering at UCLA and also a member of CNSI, along with Thomas Mason and their teams, succeeded in creating, for the first time, stable sub-hundred nanometer double nanoemulsions. According to Deming, these nanoemulsions can be made as small as 10 nm in diameter and are stable for long-term storage at room temperature. More surprising, they even remain fairly stable when autoclaved. "We can also make them in micron size, 20 micron to 50 micron in diameter. Very big size range," he added.
Explaining the structure of WOW nanoemulsions, Deming said, "We have a water droplet entrapped inside an oil droplet," in a water environment. "They are made up of amino acids, so they are similar to proteins in that respect." It means, despite their structural stability, WOW nanoemulsions can be broken down enzymatically and should be bio-resorbable in the body.
In the Nature paper, Deming and colleagues used lysine polymers for the hydrophilic component and leucine for the oil (hydrophobic) component. Discussing safety issues, Deming said, "Lysine can be toxic, but we can make them with glutamic acid, which are very non-toxic. And [for] the oil phase, we can use natural food oil like sunflower oil or olive oil, so those are also not a problem."
The most exciting thing, according to both Boystak and Deming, is that these nanoscale containers can be loaded with both water-soluble and water-insoluble drugs. Both also mentioned that WOW's properties are tunable, based on the delivery mechanism and the delivery target of a particular drug. "Obviously, the objective here is to deliver, in a highly targeted way and in a very precise dose. In some cases, in [a] smaller dose than what [would] otherwise be required," Boystak said.
Indeed, as the next step of their research effort, Deming and his team currently is fine-tuning the nanoemulsions "so we put things like targeting groups on them, and also put in some responsiveness, so they could pop open under certain stimuli," he said.
In addition to the double nanoemulsions NanoPacific has in its portfolio, it also holds exclusive rights from CNSI for mesoporous silica-based nanoparticles and a popypeptide technology. For biomedical purposes, Boystak said, NanoPacific intends to focus both on the diagnostic side (in particular diagnostic imaging) and on the therapeutic side.
The company's three big therapeutic programs include: topical applications for dermatology; acute indications, with cardiology as a possible target; and chronic indications in oncology, such as for breast, prostate and colon cancer.
"We haven't fully developed our timeline ... We think the topical application will have the shortest timeline," Boystak noted, "For example, incorporating antimicrobials for treating certain dermatological disorders [may] have the shortest pathway."
NanoPacific's intended programs are all still in the preclinical phase. "We are [doing] the PK [pharmacokinetic] and toxicity studies right now. We anticipate those will get done in the course of the next six months," he said.
Boystak commented that the corporate strategy is to work with existing FDA-approved therapeutics. "We obviously have to get this [method] approved by the FDA, but we intend to incorporate existing approved therapeutic agents into these." He exclaimed, "[Our] nanodelivery mechanism will revolutionize drug delivery."
Asked whether the technology will be appropriate to deliver siRNA or microRNA, he mentioned that NanoPacific is in discussions with an unnamed major academic medical center to look at applications with microRNA.
According to Boystak, there are about eight people involved with the company on a regular basis, divided between its management, including Vice Chairman and co-CEO Michael Flesch, and its scientific team. "We are trying to maintain as lean of a structure as possible. We have entered a research agreement with UCLA, and we also intend to work with an outside lab to accelerate the development of our programs," he said.
NanoPacific is funded internally through Brightwaters Capital, a private equity investment firm, for which Boystak is also president/CEO, and other associated investors he declined to name. He also would not disclose the amount of money raised so far, but noted, "We're comfortable that we've found adequate research capital for the next two years."