Nano-Aerosol Technology for the Diagnosis and Treatment of Smoking-related Diseases
Professor Dr. Noor Hayaty Abu Kasim
Cigarette smoking is known as the leading preventable cause of pulmonary diseases such as lung cancer and chronic obstructive pulmonary disease (COPD). Approximately 90% of lung cancer and 80% of COPD cases are linked to the cigarette smoking. Lung cancer has been the most common form of cancer in the world for a number of decades, accounting for annual 1.38 million deaths and 1.61 million new cases. COPD is also estimated to affect more than 235 million people worldwide and expected to move from the fifth to the third lethal disease by 2030. COPD which accounts for 8.6% of all deaths worldwide according to the World Health Organization (2012), is characterized by the presence of chronic, progressive, and irreversible airways obstruction associated with an abnormal inflammatory reaction in response to exposure to noxious gases.
Currently, chemotherapeutics and corticosteroids are respectively the most widely employed pharmaceutics for long-term treatment of lung cancer and COPD. These medications could be delivered via the intravenous, transdermal, ocular, nasal and pulmonary routes. However, drug delivery from the pulmonary route is the preferred approach for treatment of pulmonary diseases due to the large alveolar surface area, thin epithelial layer, high vascularization, and low proteolytic activity in the alveolar space. In this method, the medications are aerosolized using pressurised metered-dose inhalers (pMDIs), dry powder inhalers (DPIs), and nebulisers in order to obtain a rapid onset of pharmaceutical action, improved local drug accumulation, minimized systemic toxicity, and avoid first-pass metabolism of pharmaceutical agents. However, due to the large particle sizes generated by these devices, the inhaled therapeutics mostly deposit in the upper respiratory tract by inertial impaction mechanism and thus, targeted drug delivery to the selected lung regions other than the airways or the lung periphery remains challenging.
The drug particle size, aerosol dispersion pattern, and inhalation efficacy are the crucial parameters which affect the success of deep lung targeting in clinical practice. An ideal pulmonary drug delivery system must be comprised of a device which acts independently from the patients’ inhalation ability and can distribute the therapeutics specifically at the target region without affecting the other parts of the respiratory system. Moreover, the therapeutic agent must comprised of nanosized particles which can deposit at alveolar region by diffusion mechanism.
Therefore, targeted administration of nanosized aerosol droplets containing functionalized smart nanoparticles into the pulmonary system could be an effective approach for localization of drug delivery and increasing the drug deposition at alveolar region. These nanoparticles can encapsulate various diagnostic and therapeutic agents such as chemotherapeutics, genes, and DNA and deliver their cargos to the alveolar space. In this “active targeting”, drug deposition could be localized by directing the droplets containing nanoparticles to the diseased region of the respiratory system using molecular or biological recognition, or external forces such as alternating magnetic field.
The aim of this program is to investigate the health impact of smoking such as lung cancer and COPD in Malaysian population. These diseases are often diagnosed late and linked with poor prognosis as early detection and treatment are challenging. Utilization of nanotechnology could be a potential approach to meet these unmet needs.
To this end, this program aims to design and develop a nano-aerosol delivery system comprised of nanosized water droplet inhalation device and superparamagnetic nanoparticles for early detection and treatment of smoking-related diseases. Computational analyses will also be conducted to predict the nanoparticles movement and drug release behavior within the respiratory system and blood circulation. Nano-aerosols will be subjected to toxicity assays and their effectiveness will be investigated both in vitro and in vivo using different techniques such as hyperpolarized magnetic resonance imaging and radioisotope agents.