The best medicine
Researchers are finding more targeted ways to get drugs directly to the source of life-threatening diseases within our bodies
July 11, 2011
Working in the pharmaceutical industry for nine years, Dr. Bill Williams became increasingly frustrated as he saw new drugs being developed to treat life-threatening diseases only to see them discontinued because the medicine wasn’t getting to the disease site.
He decided to change jobs and do something about the problem.
Williams is one of several University of Texas at Austin College of Pharmacy faculty and researchers from other disciplines who are on the cutting edge in drug delivery, the method or process of administering medicine.
The effects of many medications are reduced before they reach the desired target in the body, Williams said. In addition, about 30 percent of drugs worldwide and more than 40 percent of newly developed pharmaceuticals have solubility issues, which means they typically cannot be absorbed well by the body.
Methods are being developed to safely shepherd drugs through specific areas of the body without damaging healthy cells, tissue and bone, and make sure the medication is better dissolved and absorbed once in the body.
To do this, scientists are turning to advances in nanotechnology.
“The research today combines pharmaceutics, chemical engineering, biomedical engineering and medicine to solve the very difficult drug delivery problems,” said Williams.
Much of the research involves modified release formulations, in which the drug is released over a period time, and targeting specific areas of the body.
“The drug may work, but can’t get to the right tissues or target organs where it needs to be,” said Williams. “Nanotechnology holds great promise for the development of targeted, localized delivery of anticancer drugs, for example, in which only cancer cells are affected and not healthy cells.”
Enhancing drug-delivery technologies can help in curing and treating diseases such as cancer, cardiovascular diseases, diabetes, fungal, respiratory and infectious diseases and treatment after organ transplants to prevent rejection.
“Our goals are improved effectiveness of drugs, reduced side effects and pain from administration of medicine and lower health care costs,” said Williams.
For most of the pharmaceutical industry’s existence, medications have primarily consisted of simple, fast-acting chemical compounds that are taken orally or as injections.
Even though the field of drug delivery now includes complex areas like DNA nanostructures, nanoparticles, biodegradable particles, polymers, liposomes, thin film freezing, polymeric micelles, quantum dots and hot melt extrusions — Associate Professor of Pharmaceutics Hugh Smyth believes the result is simple.
“Drug delivery research is an exciting field because it can turn poor drugs into great drugs, and it can happen fast to impact lives.”
Smyth is working to develop new drug delivery methods to the lungs, helping in the fight against such lung diseases as cystic fibrosis, tuberculosis, asthma, chronic obstructive pulmonary disease and chronic lung infections.
“We focus on getting drugs to the lungs and then controlling them once they’re inhaled,” he said.
When particles are deposited in the lungs, cells called macrophages rapidly remove them.
“This is ideal when we inhale dust, but for drugs it means their effectiveness is significantly removed, and patients require more frequent dosing and encounter more side effects,” Smyth said.
His lab is working on a delivery system that will evade the macrophages.
One of the major reasons for the poor life expectancy of those with cystic fibrosis is the inability of drugs to get to the lung cells responsible for the symptoms.
“The gene that leads to cystic fibrosis was discovered 20 years ago so losing patients to the disease is especially tragic since we know what causes it and what could be effective in treating it, but we can’t break through the barriers,” Smyth said.
His research works to break open or “knife” through the sticky secretions so that gene therapies and drugs to treat symptoms can get to the cells. Assisted by nano-scale magnetic particles and magnetic fields, research has shown drugs can be pulled through the sticky secretions.
“Seeing something go from my lab to a patient is the motivating force and the excitement for us,” Smyth said. “When we meet patients, like those with cystic fibrosis, we find out about their lives, including what they would like to change about their medication. The patients are inspiring, making it easy for us to go to work early and stay late.”
Dr. Jason McConville, assistant professor of pharmaceutics, is working on a new delivery system for lung cancer drugs.
“Targeting the drug directly to the lungs with an inhalant instead of the usual intravenous method for chemotherapy would hopefully have fewer side effects and improved comfort for cancer patients since the treatment would be needle-free,” McConville said, noting that the effects of the drug also are decreased when using the usual intravenous method.
“Potential effects are diluted if the drug is not delivered directly to the tumor. And, if we inhale it directly to the tumor site then we would need to take less drug which should result in much less side effects.”
McConville believes a drug that can be nebulized or administered in the form of a mist inhaled into the lungs is the answer for lung cancer treatment. One of the key aspects of his work has been to develop a formulation that can be nebulized continuously for at least 15 minutes from an electronic micropump nebulizer that is suitable for patient use.
“There has been a general trend in improving the prognosis for many cancer sufferers, but improvements in lung cancer treatments remain elusive,” he said. “Because of the challenges associated with lung cancer, I have made it a priority in my research.”
Another university pharmacy researcher, Dr. Nathan Wiederhold, is working to administer antifungal drugs in a more effective fashion for patients with pulmonary fungal infections.
“Due to the increase in death rates associated with these infections in the last 20 years, much attention is being focused in this area,” said Wiederhold.
“Fungi are responsible for causing serious infections in certain at-risk patients, including those who are undergoing chemotherapy for cancer treatment, patients who have received organ transplants and those receiving medications that may lower their immune system making them vulnerable for these types of infectious diseases,” he said.
Some of the most difficult fungal infections to treat occur within the lung because this is the site of entry into the body.
“The resulting fungal pneumonia that occurs in patients is difficult to treat and can cause significant complications,” said Wiederhold. “In addition, many of the drugs used treat the infections have certain limitations, they are difficult for the patient to take and have significant toxicities associated with them.”
Wiederhold is testing new formulations of antifungal drugs, including those that can be directly administered to the lungs.
“The ultimate goal is to overcome the shortcomings of the currently available drugs and improve treatment for patients,” he said.
At the forefront of these technological advancements is the training of numerous graduate students and postdoctoral fellows, said Williams.
“These students are now out in the pharmaceutical and chemical industries changing the way insoluble drugs are delivered,” he said. “This is the impact of their education here.”
All of the work in drug delivery research at the university is moving from basic science discovery to drug patents and eventual clinical practice. Several of the faculty members have started new companies.
Smyth recently started a small company, Respira Therapeutics, to enable his discoveries, particularly a new inhaler device, to be further developed, reach patients and ultimately obtain Federal Drug Administration approval.
“We have totally revolutionized the inhaler, making it much more efficient in delivering drugs,” said Smyth. “Instead of only 20-30 percent of the drug reaching the lungs due to poor performance, we are able to get 70-80 percent of the drug deposited.”
Small children, the elderly and those patients with lower lung function also can use the new inhaler.
In the effort to develop new processes that target drugs and enhance the therapeutic effects of insoluble pharmaceuticals, Williams created a company called Enavail that provides particle engineering expertise to re-formulate drugs for its client companies. It was founded on the pioneering research of Williams, Dr. Jay Peters of the College of Pharmacy and the University of Texas Health Science Center at San Antonio and Dr. Keith Johnston of the Cockrell School of Engineering.
The company is commercializing the technologies and has two products in clinical studies.
“With state-of-the-art research facilities located in Austin, Enavail provides particle engineering expertise for pharmaceutical, biotech and nutrition-based companies,” said Williams.
Enavail has used its technology to re-formulate drugs and developed its own drug pipeline of improved anti-fungal and immunosuppressant drugs. A safety clinical trial for 21 volunteers for one of the drugs was recently completed in San Antonio. The next trial will focus on the ability of a reformulated drug in the prevention of rejection in lung transplantation.
“The future of drug delivery must meet the challenges of future medicines,” said Williams. “Drug delivery technologies can be used to expand markets for existing products as well as to develop new medicines.”