Delivery of Cytotoxic Drugs
At the University of Texas Health Sciences Center at Houston, Ennio Tasciotti, Ph.D., assistant professor in the department of nanomedicine and biomedical engineering and the graduate school for biomedical sciences, has developed a “bio-inspired nanotechnology platform” to deliver cytotoxic drugs or imaging agents to cancer sites more effectively than existing platforms and with fewer side effects.
Dr. Tasciotti explained that by using a multistage silicon nanoparticle delivery system injected subcutaneously, 90% of the drug payload is delivered directly to the target, with only 10% remaining in the bloodstream after six hours.
Traditional delivery methods, in contrast, deliver approximately 10% of the payload to the tissue, thereby contributing to adverse side effects. Within 24 hours, the body’s natural trophism causes 100% of the injected dose of multistage silicon particles to accumulate at the tumor site.
Recent work by Dr. Tasciotti has focused on tight targeting using adipose stromal stem cells derived from human white adipose tissue. By using a patient’s own adipose stem cells, “there’s no rejection and they can be harvested easily with liposuction,” he reported.
“This controlled-release system functions as a Trojan horse, decoupling the homing and therapeutic responsibilities onto separate components.” Basically, diagnostic or therapeutic nanovectors are loaded into the pores of silicon particles, which are decorated with stem cells. Because stem cells respond to the site of inflammation to trigger healing, they are used as targeting agents, Dr. Tasciotti added.
“Stem cells find the tumor site very effectively and accumulate at the tumor.” The silicon shields the nanoparticles from the reticular endothelium system, thus minimizing side effects.
The technology has been used to target Kaposi’s syndrome, but it is still in its early stages of development. The next step, Dr. Tasciotti said, is to prove good accumulation of the nanoparticles and that they release the drugs at the right time and place before moving to preclinical trials.
One of the challenges in designing nanomaterials that are efficacious for clinical use is the nanoparticles themselves. Historically, it has been difficult to design nanoparticles in which multiple substances are distributed uniformly throughout the particle and then to produce those nanoparticles with a consistent size and shape.
Singapore-based NanoMaterials Technology has overcome that with high gravity controlled precipitation (HGCP). “We can control the size, the shape, and even the crystallinity,” claimed Jimmy Yun, Ph.D., CEO. “We are talking about particle design,” not merely manufacturing nanoparticles. This method ensures the uniform mixing of two solutions, so nucleation can be controlled.
NanoMaterials’ particles are of uniform quality, size, distribution, particle shape, and morphology. Therefore, Dr. Yun explained, their contents behave more predictably than when carried by particles in which the solutions mixed unevenly, which is inherent in manual mixing methods.
In comparing dissolution rates of gravity-controlled precipitation particles with those of spray-dried active ingredients, Dr. Yun said that 80% of the HGCP particles dissolved within 10 minutes, compared to only 20% of the spray-dried particles.
Aerosol performance tests comparing NanoMaterials’ spherical nanoparticles to microsized APIs showed that the total fine-particle fraction for the nanoparticles was nearly 85%, compared to 35% for the microparticles. Additional applications include using these nanoparticles as a controlled-release technology for therapeutics and to induce hyperthermia for tumors (which do not dissipate heat as readily as normal cells).
The company is working at the industrial scale, designing particles as small as 10 nm. The first pharmaceutical pilot plant using HGCP technology can produce 40 tons of antibiotics per year, according to Dr. Yun, and the first commercial production facility can produce 10,000 tons per year.
NanoMaterials just signed a deal to develop particles for a product destined for the FDA-approval process and also has signed a license agreement with a Chinese pharmaceutical firm to develop the particles for State Food and Drug Administration approval.