In vivo safety and particokinetics of inhaled nanomedicines
Lead Research Organisation:
King's College London
Department Name: Pharmaceutical Sciences
Abstract
Inhalation is a swift and painless way to administer medicines to a patient. To make inhaled medicines work more efficiently, exhibit fewer side effects and cost less, inhalation researchers are developing ways to prevent drugs from escaping the lung too quickly, which can weaken their therapeutic effect. One of the most promising ways to keep the drug in the lung longer is to load it into very tiny capsules, which are inhaled and then able to release the drug in a slow and controlled manner. When the carrier is emptied, it will dissolve and disappear from the lung without producing any harmful side effects itself. It is thought that drug carriers in the nanometer size range (this is about 1000 times thinner than a human hair) remain in the lung longer than larger carriers and are therefore best suited for inhaled medicines. Due to their size, these drug carriers belong to a larger group of small particles known in general as nanoparticles.
Inhaling some types of nanoparticles, especially those that are a product of combustion and are a component of air pollution, can be dangerous. Environmental toxicologists have been studying the health effects of inhaling industrial or environmental nanoparticles for many years now. They have found that many nanoparticles are particularly harmful to lungs, causing short-term inflammation and long-term an increase in the risk of lung cancer.
Nanoparticle drug carriers have little to do with toxic industrial or environmental nanoparticles. They are made from materials that are considered to be ?safe? for human consumption and most importantly, will dissolve and disappear from the lung. However, many things are still unknown about the effects of these drugs carriers after inhalation. Therefore, the aim of our study is 1) to investigate how long medicinal nanoparticles will remain in the lung after inhalation and 2) whether inhalation of these particles causes any measurable reaction in the lung, which may be a potential safety concern.
It is our view that these basic questions need to be addressed before such nanoparticle carriers can be considered safe and useful components of inhaled medicines. Answers to these questions would provide extremely useful guidelines for drug delivery scientists designing innovative nanomedicines and could greatly enhance the speed with which important new medicines may reach the patient.
Inhaling some types of nanoparticles, especially those that are a product of combustion and are a component of air pollution, can be dangerous. Environmental toxicologists have been studying the health effects of inhaling industrial or environmental nanoparticles for many years now. They have found that many nanoparticles are particularly harmful to lungs, causing short-term inflammation and long-term an increase in the risk of lung cancer.
Nanoparticle drug carriers have little to do with toxic industrial or environmental nanoparticles. They are made from materials that are considered to be ?safe? for human consumption and most importantly, will dissolve and disappear from the lung. However, many things are still unknown about the effects of these drugs carriers after inhalation. Therefore, the aim of our study is 1) to investigate how long medicinal nanoparticles will remain in the lung after inhalation and 2) whether inhalation of these particles causes any measurable reaction in the lung, which may be a potential safety concern.
It is our view that these basic questions need to be addressed before such nanoparticle carriers can be considered safe and useful components of inhaled medicines. Answers to these questions would provide extremely useful guidelines for drug delivery scientists designing innovative nanomedicines and could greatly enhance the speed with which important new medicines may reach the patient.
Technical Summary
Nanoparticle-based vehicles that deliver drugs to or via the lung provide an innovative solution to many deficits currently associated with inhaled therapies. The focus of scientific effort has been on improving the design and characterisation of nanoparticle drug delivery systems, while in vivo particokinetics (i.e. fate of the nanoparticulate drug carrier in the lung) and safety remain largely unexamined. This is astounding given the relatively large body of knowledge accumulated by environmental scientists on the toxicology of airborne nanoparticle systems. Against this backdrop, the proposed programme aims to to address the fundamental questions arising from the increased interest in inhaled nanoparticulate drug delivery vehicles: How do nanomedicines interact with the lung after inhalation? Does the composition of the vehicle dictate its retention and clearance profiles? Do inhaled biodegradable nanoparticulate drug carriers cause an undesired or harmful response in the lung? If so, what are the nanoparticle properties responsible for this response? Is it possible to predict which types of nanoparticle materials will be safe for medicinal use? The premise of this study is that the in vivo particokinetics and pulmonary toxicity of inhaled nanoparticle drug carrier systems can be related to their physical and chemical properties.
The design of this programme closely follows the recommendations put forth in the Defra-sponsored report on ?Characterising the Potential Risks posed by Engineered Nanoparticles?. However, although ?medical, health and personal care applications of nanotechnologies? are briefly alluded to in the report, its focus is centred exclusively on the risk assessment of industrial and reference NP. It is of great concern that more recognition has not been allocated to the need for risk assessment of inhaled nanomedicines (and specifically drug delivery vehicles) as well as for the investigation of any specific toxicity mechanisms related to this special group of NP. The conception of this programme is a deliberate attempt to address what is perceived to be a gap in current nanotoxicology initiatives.
The design of this programme closely follows the recommendations put forth in the Defra-sponsored report on ?Characterising the Potential Risks posed by Engineered Nanoparticles?. However, although ?medical, health and personal care applications of nanotechnologies? are briefly alluded to in the report, its focus is centred exclusively on the risk assessment of industrial and reference NP. It is of great concern that more recognition has not been allocated to the need for risk assessment of inhaled nanomedicines (and specifically drug delivery vehicles) as well as for the investigation of any specific toxicity mechanisms related to this special group of NP. The conception of this programme is a deliberate attempt to address what is perceived to be a gap in current nanotoxicology initiatives.