ALD coating for delayed drug delivery via the lungs for the treatment of respiratory diseases by Astra Zeneca and TU Delft

The medical thin film coating segment is a mature and growing market for CVD & PVD coating equipment and ALD is an emerging segment. Applications are :

• electronic implants (IC, BioMEMS, Pacemaker) 
• prosthetic implants (spine, trauma, hip, knee, dental)
• active pharmaceuticals ingredients for  delayed drug delivery

ALD has slowly but steadily moved into the field of medical and pharmaceuticals. Just as some examples Nanxa AB in Sweden and Applied Materials has a joint venture and Picosun in Finland and Veeco has very active business unit and offer ALD systems specifically for medical applications for several years. As well as several reports on applications such as dental, tissue engineering, smart lenses, and various electronic or prosthetic implants.

Here is a new application explored by Dutch TU Delft and British-Swedish Astra Zeneca using ALD coating for delayed drug delivery via the lungs for the treatment of respiratory diseases.

Controlled Pulmonary Delivery of Carrier-Free Budesonide Dry Powder by Atomic Layer Deposition

ACS Nano 2021, XXXX, XXX, XXX-XXX

Publication Date:March 26, 2021, https://doi.org/10.1021/acsnano.0c10040

Ideal controlled pulmonary drug delivery systems provide sustained release by retarding lung clearance mechanisms and efficient lung deposition to maintain therapeutic concentrations over prolonged time. Here, we use atomic layer deposition (ALD) to simultaneously tailor the release and aerosolization properties of inhaled drug particles without the need for lactose carrier. In particular, we deposit uniform nanoscale oxide ceramic films, such as Al2O3, TiO2, and SiO2, on micronized budesonide particles, a common active pharmaceutical ingredient for the treatment of respiratory diseases. In vitro dissolution and ex vivo isolated perfused rat lung tests demonstrate dramatically slowed release with increasing nanofilm thickness, regardless of the nature of the material. Ex situ transmission electron microscopy at various stages during dissolution unravels mostly intact nanofilms, suggesting that the release mechanism mainly involves the transport of dissolution media through the ALD films. Furthermore, in vitro aerosolization testing by fast screening impactor shows a ∼2-fold increase in fine particle fraction (FPF) for each ALD-coated budesonide formulation after 10 ALD process cycles, also applying very low patient inspiratory pressures. The higher FPFs after the ALD process are attributed to the reduction in the interparticle force arising from the ceramic surfaces, as evidenced by atomic force microscopy measurements. Finally, cell viability, cytokine release, and tissue morphology analyses verify a safe and efficacious use of ALD-coated budesonide particles at the cellular level. Therefore, surface nanoengineering by ALD is highly promising in providing the next generation of inhaled formulations with tailored characteristics of drug release and lung deposition, thereby enhancing controlled pulmonary delivery opportunities.