Tag Archives: lung diseases

University of Malaya (Malaysia) and Harvard University (US) partner on nanomedicine/prevention projects

Unusually for a ‘nanomedicine’ project, the talk turned to prevention during a Jan. 10, 2016 teleconference featuring Dr. Noor Hayaty Abu Kasim of the University of Malaya and Dr. Wong Tin Wui of the Universiti Teknologi Malaysia and Dr. Joseph Brain of  Harvard University in a discussion about Malaysia’s major investment in nanomedicine treatment for lung diseases.

A Jan. 11, 2016 Malaysian Industry-Government Group for High Technology (MIGHT) news release on EurekAlert announces both the lung project (University of Malaya/Harvard University) and others under Malaysia’s NanoMITe (Malaysia Institute for Innovative Nanotechnology) banner,

Malaysian scientists are joining forces with Harvard University experts to help revolutionize the treatment of lung diseases — the delivery of nanomedicine deep into places otherwise impossible to reach.

Under a five-year memorandum of understanding between Harvard and the University of Malaya, Malaysian scientists will join a distinguished team seeking a safe, more effective way of tackling lung problems including chronic obstructive pulmonary disease (COPD), the progressive, irreversible obstruction of airways causing almost 1 in 10 deaths today.

Treatment of COPD and lung cancer commonly involves chemotherapeutics and corticosteroids misted into a fine spray and inhaled, enabling direct delivery to the lungs and quick medicinal effect. However, because the particles produced by today’s inhalers are large, most of the medicine is deposited in the upper respiratory tract.

The Harvard team, within the university’s T.H. Chan School of Public Health, is working on “smart” nanoparticles that deliver appropriate levels of diagnostic and therapeutic agents to the deepest, tiniest sacs of the lung, a process potentially assisted by the use of magnetic fields.

Malaysia’s role within the international collaboration: help ensure the safety and improve the effectiveness of nanomedicine, assessing how nanomedicine particles behave in the body, what attaches to them to form a coating, where the drug accumulates and how it interacts with target and non-target cells.

Led by Joseph Brain, the Cecil K. and Philip Drinker Professor of Environmental Physiology, the research draws on extensive expertise at Harvard in biokinetics — determining how to administer medicine to achieve the proper dosage to impact target cells and assessing the extent to which drug-loaded nanoparticles pass through biological barriers to different organs.

The studies also build on decades of experience studying the biology of macrophages — large, specialized cells that recognize, engulf and destroy target cells as part of the human immune system.

Manipulating immune cells represents an important strategy for treating lung diseases like COPD and lung cancer, as well as infectious diseases including tuberculosis and listeriosis.

Dr. Brain notes that every day humans breathe 20,000 litres of air loaded with bacteria and viruses, and that the world’s deadliest epidemic — an outbreak of airborne influenza in the 1920s — killed tens of millions.

Inhaled nanomedicine holds the promise of helping doctors prevent and treat such problems in future, reaching the target area more swiftly than if administered orally or even intravenously.

This is particularly true for lung cancer, says Dr. Brain. “Experiments have demonstrated that a drug dose administered directly to the respiratory tract achieves much higher local drug concentrations at the target site.”

COPD meanwhile affects over 235 million people worldwide and is on the rise, with 80% of cases caused by cigarette smoking. Exacerbated by poor air quality, COPD is expected to rise from 5th to 3rd place among humanity’s most lethal health problems by 2030.

“Nanotechnology is making a significant impact on healthcare by delivering improvements in disease diagnosis and monitoring, as well as enabling new approaches to regenerative medicine and drug delivery,” says Prof. Zakri Abdul Hamid, Science Advisor to the Prime Minister of Malaysia.

“Malaysia, through NanoMITe, is proud and excited to join the Harvard team and contribute to the creation of these life-giving innovations.”

While neither Dr. Abu Kasim nor Dr. Wong are included in the news release both are key members of the Malaysian team tasked to work on nanomedicines for lung disease. Dr. Abu Kasim is a professor of restorative dentistry at the University of Malaya and familiar with nanotechnology-enabled materials and nanoparticles through her work in that field. She is also the project lead for NanoMITe’s Project 4: Consequences of Smoking among the Malaysian Population. From the project webpage,

Smoking is a prevalent problem worldwide but especially so in Asia where nearly more than half of the world population reside. Smoking kills half of its users and despite the many documented harm to health is still a major problem. Globally six million lives are lost each year because of this addiction. This number is estimated to increase to ten million within the next two decades. Apart from the mortality, smokers are at increased risk of health morbidities of smoking which is a major risk factor for many non-communicable diseases (NCD) such as heart diseases, respiratory conditions and even mental health. Together, smoking reduces life expectancy 10-15 years compared to a non-smoker. Those with mental health lose double the years, 20 -25 years of their life as a result of their smoking. The current Malaysia death toll is at 10,000 lives per year due to smoking related health complications.

Although the health impact of smoking has been reported at length, this information is limited nationally. Lung cancer for example is closely linked to smoking, however, the study of the link between the two is lacking in Malaysia. Lung cancer particularly in Malaysia is also often diagnosed late, usually at stages 3 and 4. These stages of cancer are linked with a poorer prognosis. As a result to the harms to health either directly or indirectly, the World Health Organization (WHO) has introduced a legal treaty, the first, called the Framework Convention for Tobacco Control (FCTC). This treaty currently ratified by 174 countries was introduced in 2005 and consists of 38 FCTC Articles which are evidence based policies, known to assist member countries to reduce their smoking prevalence. Malaysia is an early signatory and early adopter of the MPOWER strategy which are major articles of the FCTC. Among them are education and information dissemination informing the dangers of smoking which can be done through awareness campaigns of advocacy using civil society groups. Most campaigns have focused on health harms with little mention non-health or environmental harm as a result of smoking. Therefore there is an opportunity to further develop this idea as a strong advocacy point towards a smoke-free generation in the near future

It is difficult impossible to recall any other nanomedicine initiative that has so thoroughly embedded prevention as part of its mandate. As Dr. Brain puts it, “Malaysia’s commitment to better health for everyone—sometimes, I’m jealous.”

Getting back to nanomedicine, it’s Dr. Wong, an associate professor in the school of pharmaceutics at Universiti Teknologi Malaysia (UTM), who is developing polymeric nanoparticles designed to carry medications into the lungs and Brain who will work on the best method of transport. From Dr. Brain’s webpage,

Dr. Brain’s research emphasizes responses to inhaled gases, particulates, and microbes. His studies extend from the deposition of inhaled particles in the respiratory tract to their clearance by respiratory defense mechanisms. Of particular interest is the role of lung macrophages; this resident cell keeps lung surfaces clean and sterile. Moreover, the lung macrophage is also a critical regulator of inflammatory and immune responses. The context of these studies on macrophages is the prevention and pathogenesis of environmental lung disease as well as respiratory infection.

His research has utilized magnetic particles in macrophages throughout the body as a non-invasive tool for measuring cell motility and the response of macrophages to various mediators and toxins. …

It was difficult to get any specifics about the proposed lung nanomedicine effort as it seems to be at a very early stage.

  • Malaysia through the Ministry of Higher Education with matching funds from the University of Malaya is funding this effort with 1M Ringgits ($300,00 USD) per year over five years for a total of 5M Ringgits ($1.5M USD)
  • A Malaysian researcher will be going to Harvard to collaborate directly with Dr. Brain and others on his team. The first will be Dr. Wong who will come to Harvard in June 2016 where he will work with his polymeric nanoparticles (vehicles for medications) and where Brain will examine transport strategies (aerosol, intrathecal administration, etc.) for those nanoparticle-bearing medications.
  • There will be a series of comparative studies of smoking in Malaysia and the US and other information efforts designed to support prevention strategies.

One last tidbit about research, Dr. Brain will be testing the nanoparticle-bearing medication once it has entered the lung using the ‘precision cut lung slices’ technique, as an alternative to some, if not all, in vivo testing.

Final comments

Nanomedicine is highly competitive and the Malaysians are interested in commercializing their efforts which according to Dr. Abu Kasim is one of the reasons they approached Harvard and Dr. Brain.

Should you find any errors please do let me know.

Gold nanorods and mucus

Mucus can kill. Most of us are lucky enough to produce mucus appropriate for our bodies’ needs but people who have cystic fibrosis and other kinds of lung disease suffer greatly from mucus that is too thick to pass easily through the body. An Oct. 9, 2014 Optical Society of America (OSA) news release (also on EurekAlert) ‘shines’ a light on the topic of mucus and viscosity,

Some people might consider mucus an icky bodily secretion best left wrapped in a tissue, but to a group of researchers from the University of North Carolina at Chapel Hill, snot is an endlessly fascinating subject. The team has developed a way to use gold nanoparticles and light to measure the stickiness of the slimy substance that lines our airways.  The new method could help doctors better monitor and treat lung diseases such as cystic fibrosis and chronic obstructive pulmonary disease.

“People who are suffering from certain lung diseases have thickened mucus,” explained Amy Oldenburg, a physicist at the University of North Carolina at Chapel Hill whose research focuses on biomedical imaging systems. “In healthy adults, hair-like cell appendages called cilia line the airways and pull mucus out of the lungs and into the throat. But if the mucus is too viscous it can become trapped in the lungs, making breathing more difficult and also failing to remove pathogens that can cause chronic infections.”

Doctors can prescribe mucus-thinning drugs, but have no good way to monitor how the drugs affect the viscosity of mucus at various spots inside the body. This is where Oldenburg and her colleagues’ work may help.

The researchers placed coated gold nanorods on the surface of mucus samples and then tracked the rods’ diffusion into the mucus by illuminating the samples with laser light and analyzing the way the light bounced off the nanoparticles. The slower the nanorods diffused, the thicker the mucus. The team found this imaging method worked even when the mucus was sliding over a layer of cells—an important finding since mucus inside the human body is usually in motion.

“The ability to monitor how well mucus-thinning treatments are working in real-time may allow us to determine better treatments and tailor them for the individual,” said Oldenburg.

It will likely take five to 10 more years before the team’s mucus measuring method is tested on human patients, Oldenburg said. Gold is non-toxic, but for safety reasons the researchers would want to ensure that the gold nanorods would eventually be cleared from a patient’s system.

“This is a great example of interdisciplinary work in which optical scientists can meet a specific need in the clinic,” said Nozomi Nishimura, of Cornell University … . “As these types of optical technologies continue to make their way into medical practice, it will both expand the market for the technology as well as improve patient care.”

The team is also working on several lines of ongoing study that will some day help bring their monitoring device to the clinic. They are developing delivery methods for the gold nanorods, studying how their imaging system might be adapted to enter a patient’s airways, and further investigating how mucus flow properties differ throughout the body.

This work is being presented at:

The research team will present their work at The Optical Society’s (OSA) 98th Annual Meeting, Frontiers in Optics, being held Oct. 19-23 [2014] in Tucson, Arizona, USA.

Presentation FTu5F.2, “Imaging Gold Nanorod Diffusion in Mucus Using Polarization Sensitive OCT,” takes place Tuesday, Oct. 21 at 4:15 p.m. MST [Mountain Standard Time] in the Tucson Ballroom, Salon A at the JW Marriott Tucson Starr Pass Resort.

People with cystic fibrosis tend to have short lives (from the US National Library of Medicine MedLine Plus webpage on cystic fibrosis),

Most children with cystic fibrosis stay in good health until they reach adulthood. They are able to take part in most activities and attend school. Many young adults with cystic fibrosis finish college or find jobs.

Lung disease eventually worsens to the point where the person is disabled. Today, the average life span for people with CF who live to adulthood is about 37 years.

Death is most often caused by lung complications.

I hope this work proves helpful.