College of Pharmacy researchers share latest insights into novel drug delivery technology

Many of us will remember that at the beginning of the pandemic, breakthrough drugs that changed the way COVID-19 was treated were hard to come by. The driving reason was that these therapies, including mRNA vaccines and monoclonal antibodies, are “biological” and often unstable at room temperature. As a result, mRNA vaccines must be stored in ultra-cold freezers and sometimes discarded at the end of the day after reconstitution, and monoclonal antibodies require a hospital environment for administration and cannot be taken home.

Access to these therapies has improved since the pandemic began, but remains a challenge. Limitations in the formulation of other biologics such as cell and gene therapies have also hampered innovation in these areas. Researchers in the laboratory of Dr. Robert O. (Bill) Williams III, Department Head and Professor of Molecular Pharmacy and Drug Delivery at the University of Texas at the Austin College of Pharmacy, is advancing an innovative platform technology called Thin Film Freezing that could improve the administration, distribution and access to vaccines and revolutionize therapies.

The one from Dr. Invented by Williams and his team and further developed by Fort Worth-based TFF Pharmaceuticals, thin-film freezing technology is developed via a well-controlled process that rapidly freezes and dries drugs into a powder. The technology is unique in that it can convert vaccines and other biological products that traditionally come in liquid form into a powder that’s more stable at room temperature, eliminating the need for ultra-cold chain refrigeration and making medicines more accessible worldwide through coping logistical challenges in distribution. The technology has broad applicability in therapeutic areas, including great potential for treating infectious diseases like COVID-19.

Thin-film freezing formulations can be injected like today’s mRNA vaccines, but also have the advantage of being inhaled or administered intranasally, which does not require a healthcare professional for administration. Intranasal formulations provide yet another benefit by targeting the mucosal system directly, tapping into key mechanisms that trigger immune defenses at the gateway where viruses enter the body to more quickly neutralize the virus at its source.

“Oral therapies for diseases of the lungs and respiratory system like COVID are an example of suboptimal drug delivery,” said Dr. Williams. “Administering these drugs in oral form usually requires a large dose to reach the target tissues in the organs and can lead to serious side effects, sometimes life-threatening. By directly targeting the point of need, our thin film freezing formulations bypass toxicity and avoid drug-drug interactions.”

dr Williams and his lab have accumulated extensive research — which continues to grow — supporting thin-film freezing as a promising technology for converting vaccines and other treatments into inhaled and intranasal forms. Scientists have also published papers and articles explaining how thin film freezing compares to other dry powder drug delivery techniques. The invention of Dr. Williams has demonstrated significant benefits as a gentler process for sensitive modalities such as proteins, DNA, mRNA and other biologics and small molecules.

Recent research published on preprint server bioRxiv showed how thin film freezing could be used to engineer dry powder versions of plasmid DNA for optimized delivery to the lungs, while another paper just published in International Journal of Pharmacy showed how the mean freezing rate of thin layer freezing resulted in less denaturation of proteins compared to spray freeze drying (SFD) and conventional freeze drying. The minimal shear forces of the process also reduce the risk of protein degradation.

dr Williams and his team even apply artificial intelligence and machine learning to improve efficiency when developing product-specific dry powder formulations. In a research paper presented at this year’s American Association of Pharmaceutical Scientists (AAPS) PharmSci 360 meeting, researchers used a deep learning-based method to estimate aerosol performance based on the properties of the powder produced by thin film freezing, specifically using of image analysis. The poster was published together with another poster by the team of Dr. Williams demonstrating the successful application of thin film freezing formulations to a range of biologic drugs including anti-SARS-CoV-2 and anti-PD1 antibodies as part of the “Special Poster Collections” at the meeting.

All of these results are good news for the future of biologic drug development and could not only aid the development of future COVID-19 therapies, but also target future pathogens as they emerge. TFF Pharmaceuticals applies this technology to a wide range of treatments, three of which are currently in clinical trials, including a dry powder version of niclosamide, a powerful antiviral that has been shown to be effective against all COVID-19 variants tested to date. TFF’s inhaled niclosamide powder was well tolerated Phase 1 trials with fewer side effects compared to the oral form of treatment.

In addition to developing therapies in-house, TFF Pharmaceuticals works with many Big Pharma, academic and CDMO partners recently opened a new facility in Austin, Texas – not far from dr. Williams’ lab removed – which provides additional space to facilitate the scaling and manufacture of dry powder materials, including for biologics, and to manufacture materials for pre-clinical studies.

“We are excited to continue to see scientific advances in the use of the Thin Film Freezing technology platform across multiple modalities across the treatment landscape through the innovative work of our employees at UT Austin,” commented Glenn Mattes, CEO of TFF. “Bill and his team’s latest research continues to demonstrate the versatile applications of thin film freezing for biologic drug development and delivery. We look forward to our continued collaboration and sharing more data through our platform in the years to come.”

While we do not know what future pandemics might look like, with recent developments in the treatment of COVID-19 and government calls for alternative methods of vaccination and treatment of contagious diseases, it is likely that inhaled and intranasal therapies will play a role. Thin film freezing technology can better prepare the industry for future pandemic preparedness and other pathogens or emerging biological threats that may arise. Further research results from the laboratory of Dr. Williams will be available shortly.

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