The progress in the administration of inhaled drugs: an interview with Dr. Robert Clarke

The progress in the administration of inhaled drugs: an interview with Dr. Robert Clarke -

insights of industry Dr. Robert Clarke

CEO 

Pulmatrix

Interview by April Cashin-Garbutt , MA (Cantab)

What are the main advantages of delivering drugs directly to the lungs by the administration of inhaled drugs?

provide medication to the lungs by inhalation has a number of potential advantages over traditional routes of administration such as pills or injections. For the treatment of lung diseases, the obvious logic that we apply is topical administration into the airways by inhalation.

Understanding where drug deposition in the respiratory tract, one can target the treatment to a specific area in the lungs and to treat a pulmonary disease on the disease site.
This also allows us the opportunity to significantly reduce the amount of drug administered to the patient as opposed to oral administration where you have to give high doses to get enough of the drug from the gastrointestinal intestinal through the bloodstream into the lung tissue. direct delivery to the lungs also avoids first-pass metabolism that can be very important for the effectiveness of the drug.
Another advantageous aspect of the lung is for systemic administration of the drug. The human lung has a very large alveolar surface which can allow quick access to the bloodstream. Inhale microscopic drug formulations provides drug to the alveoli where drugs can easily enter the bloodstream.
An inhaled formulation to the appropriate dose can provide intravenous pharmacokinetic profile with corresponding peak concentrations, time to peak levels and similar exposure over time.

Please can you give a brief history of inhaled drug delivery techniques?

inhaling deliver drugs in the airways is known since antiquity. Nebulizers have long been used to deliver liquid aerosols to the patient's airways. The invention of the metered dose inhaler (MDI) in the 1940s really inspired the idea of ​​a portable handheld inhaler devices. These are the typical "asthma inhalers" we're all familiar with that produce tiny droplets of aerosol that can be inhaled.

DPIs lactose-based media (DPI-LB) came the following long. With this dry powder technology, micronised drug is adsorbed on the surface of a large lactose carrier. When the patient inhales, theoretically, the drug comes off the lactose surface and is aerodynamically small enough to travel in the patient's airway while lactose land in the back of the throat and swallowed.
The MDI and DPI- LB technologies have been the basis of a number of very effective products to patients. However, these technologies are limited by the types of drugs that may be used, doses that can be delivered, and the efficacy of the suboptimal delivery.
This led engineers in the late 0s to think of different ways to do better dry powders having improved delivery characteristics. Large porous particles such as AIR and Nektar Pulmospheres technology allowed scientists to consider a much wider range of drugs for pulmonary administration.
These powders provide more effective drugs and because of the way they are made, higher doses can be delivered in each inhalation. These formulations can provide three times more medication or even higher compared to DPI-LB. This opened the universe to administer pulmonary drugs.
In Pulmatrix, we bring forward the approach of next generation engineering. Our iSPERSE technology is a dry powder designed with a density profile above that of previous technologies, but with all the same benefits delivery.
Combining this with our expertise around the nano-sized drug particles that can be combined in our iSPERSE formulations, we can consider almost all drugs for pulmonary administration of drugs.

What conditions would especially benefit from the administration of inhaled drugs?

There are a variety of lung diseases that may benefit from the administration of drugs by inhalation. COPD and asthma were served by inhaled drugs for decades and are very large patient populations that still have significant unmet needs.
The rare disease of cystic fibrosis using a number of inhaled drugs with a number in development. Other rare lung diseases such as idiopathic pulmonary fibrosis are currently treated with oral formulations and inhalation seems like an obvious direction to do.
The scientists examined the local treatment of lung cancer by inhalation. Essentially, the list of lung disease could be considered
If we consider the systemic conditions that could benefit from a rapid exposure of the drug in the bloodstream, the list includes all areas of major disease. Metabolic, reproductive, pain, neuropsychiatry, cardiovascular.

What are the limits to deliver drugs to the lungs with nebulizers?

nebulizers have long been used by patients and patients in the home setting. But they are not ideal for patients which is why all other technologies have come along.
nebulizers typically have a low efficiency. What this translates to patients are dosed over time where they should wear a mask or breathing on a mouthpiece for long periods of time, usually several tens of minutes depending on the dose.
The amount of medication wasted over the dosing period is quite high, which may matter to the side effects and cost of goods. Another challenge is the nature of a single dose nebulizers which require regular cleaning unlike other technologies.

Could you please preview the iSPERSE patented engineering technology Pulmatrix particles?

iSPERSE is a dry powder engineering technology particles made by spray drying allows us to consider the formulation of almost all classes of drugs in a form easily inhaled. The feature of the technology is small, dense and dispersible resulting in the patent novelty and different technology other engineering technologies particles (eg Nektar Pulmospheres).
Highlights iSPERSE are 1) high efficiency of delivery deliver 3X or more inhaled drugs than traditional technologies; 2) the flow rate independence means that patients with compromised lung function can still easily and reproducibly receiving their dose; 3) a higher dose will allow inhalation treatment with drugs that require higher doses; and 4) the ability to formulate virtually any class of drugs from small molecules and combinations across biological products, including nucleic acids, peptides, proteins, and even antibodies.
And because of the higher density profile differentiation iSPERSE other engineered low density powders, the technology can work with any dry powder inhaler device, -capsule, reservoir-, or based on blisters.

What limits does solve iSPERSE?

We look iSPERSE that improved approaches today, while enabling new approaches for tomorrow. Due to the high efficiency delivery iSPERSE, we can make better drug inhaled versions currently based nebulizers, MDI or DPI-LB.
In terms of new approaches, iSPERSE allows us to consider inhaling molecules have generally not been considered or required long sprays. technology MDI / DPI can provide low microgram quantities mg of drug per inhalation limiting to powerful molecules.
But iSPERSE can provide tens of milligrams per inhalation. This opens all classes of drugs that could provide iSPERSE inhaled. Our current pipeline uses this capability to our inhaled antifungal and our undisclosed projects of idiopathic pulmonary fibrosis.

What impact do you think the administration of drugs by inhalation may have on antimicrobial resistance?

In the case of our antifungal inhalation, local administration of an overwhelming dose of the antifungal agent, the more overwhelming in terms of fungal eradication, should reduce concerns about the development of resistance .
resistance concerns are generally associated with threshold therapeutic doses may allow a bug to "escape" antimicrobial activity. These exhaust bugs can then become resistant. By providing a dose larger than the threshold, we should reduce this concern.

What do you think the future for the administration of drugs by inhalation and what is the vision of Pulmatrix?

We believe that the administration of inhaled drugs will continue to grow as an approach for the treatment of diseases both local and systemic. We learned some market research that many patients like ease of use, portability and route of delivery to avoid gastrointestinal effects of many drugs. We look forward to being at the forefront of engineering of these approaches starting with our current pipeline.

where readers find more information?

Our website is www.pulmatrix.com

About Dr. Robert Clarke

Dr. Clarke was promoted to CEO of Pulmatrix in 2012 after having served as Chief scientific Officer. Joining Pulmatrix in 04 as the first Ph.D. scientific level, its role has evolved to monitoring efforts in research and development at Pulmatrix focused on the development of Pulmatrix technologies for the treatment of respiratory diseases.
He raised over $ 60 million in funding from venture capital for the company as well as got more non-dilutive financing of $ 10 million to support R & D programs Pulmatrix Before Pulmatrix, he was associate Director for life sciences at Alkermes, Inc. focused on the development of inhaled therapeutics with the technological platform AIR®.
Dr. Clarke holds a B.Sc. in biomedical engineering from the University of Boston, has a doctorate in physiology from Johns Hopkins University and completed his post-doctoral training in biology breathing at Brigham and Women's Hospital and Harvard University. Dr. Clarke has over a dozen years industry and over 20 years of total experience focused on pulmonary administration of drugs and the role of inhaled particles in respiratory biology and medicine of the first co-author plan more 80 chapters, articles and abstracts.