John M. Prausnitz AIChE Institute Lecture

The Executive Board of the Program Committee invites a distinguished member of AIChE to present a comprehensive authoritative review of the chemical engineering science in his or her field of specialization. Selection criteria include:

1. the quality and relevance of the accomplishments of the lecturer in the technical field likely to be the subject of the lecture
2. the communication skills of the lecturer
3. the value of the lecture to the meeting attendees and the members of the Institute

To honor Dr. John M. Prausnitz of the University of California, Berkeley's exceptional impact on the profession, society, and generations of chemical engineering students, AIChE’s Board of Directors has agreed to rename the Institute Lecture to the John M. Prausnitz AIChE Institute Lecture. The AIChE Foundation gratefully acknowledges the generosity of John’s closest peers who have made lead gifts to establish an endowment to support the Lecture and ensure John’s name will be recognized in perpetuity.

This is the 75^th AIChE Institute Lecture.

Supported by the AIChE Foundation.

This year's John M. Prausnitz AIChE Institute Lecturer is Mark R. Prausnitz, Regents’ Professor, Regents’ Entrepreneur and J. Erskine Love, Jr. Chair in Chemical & Biomolecular Engineering, Georgia Institute of Technology.

Translation of biomedical microtechnologies from the lab to the clinic

Mark R. Prausnitz, Regents’ Professor, Regents’ Entrepreneur and J. Erskine Love, Jr. Chair in Chemical & Biomolecular Engineering, Georgia Institute of Technology

Many tissue barriers that limit access to the body exist on the micron length scale. We are therefore developing microtechnologies that selectively cross these barriers in a minimally invasive way to improve drug delivery and other medical applications. In some cases, this approach can target drug delivery to specific tissues. In other cases, this approach simplifies drug delivery for increased patient access and acceptability. In all cases, we emphasize technologies that are simple to use, are inexpensive to produce, and improve safety, efficacy and/or access to medical treatments. 

Vaccination generally requires injection by needle and syringe. This method often limits access to vaccines in developing countries for lack of trained health care providers; limits compliance with influenza, COVID and other vaccinations due to patient hesitancy to be injected; limits safety because of inherent dangers of needlesticks and biohazardous sharps waste; and limits immunogenicity by vaccinating typically in the muscle, which often provides inferior immune responses compared to vaccination in skin and mucosal tissues. To address these limitations, we are developing microneedle patches for vaccination. These patches contain arrays of solid, conical microneedles made of a mixture of vaccine and safe, water-soluble materials. When pressed to the skin, the microneedles dissolve in the dermal fluids within a few minutes to release the vaccine. Microneedle patches can increase access to vaccination because little to no expertise is needed to administer them.  They can improve vaccination compliance because they are painless and convenient. They can improve safety because the microneedles dissolve in the skin, leaving no sharps waste. And they can improve immune responses by targeting vaccine delivery to the immune cells of the skin. We have developed microneedle patches to achieve these various capabilities, and have developed them through design, fabrication, in vitro characterization, and in vivo immunogenicity studies, including human clinical trials

Some vaccines, like the mRNA vaccines used to combat the COVID-19 pandemic, need to be delivered into cells. Current mRNA vaccines accomplish this using lipid nanoparticle delivery systems, but these formulations are complex, costly and may be associated with side effects. Electroporation is a well-established way to deliver nucleic acids into cells in the lab using short electric pulses, but its use for human vaccination is limited by high cost, complex instrumentation and painful delivery. We developed a novel electroporation device that generates pulses using a low-cost piezoelectric element combined with microneedle electrodes that limit the electric field to the cells found in the skin’s epidermis. In this way, we have achieved electroporation that was effective to administer a DNA vaccine against SARS-CoV-2 in mice using a device expected to cost less than $1.00 that was reported as painless by human subjects. 

Microneedle patches are effective to breach the skin barrier, but are difficult to use on large areas of skin, as might be needed in dermatology or cosmetics. We therefore developed STAR particles, which are millimeter-scale particles with microneedles sticking out. When rubbed on the skin, the STAR particles make micropores in the skin through which drugs can diffuse. STAR particles were effective to increase skin permeability to dermatological drugs by one to two orders of magnitude in vitro, improved treatment of melanoma by topical chemotherapy in mice, and were found to be painless and well-tolerated in human subjects, even after repeated use. 

Most biomarkers of use in clinical medicine are collected from blood, but blood is only about 7% of bodily fluids. Interstitial fluid (ISF), which is the extracellular fluid bathing cells in tissues, is more than 20% of bodily fluid and contains both systemic as well as local tissue biomarkers. It also does not clot or contain cells, which facilitates continuous or repeated measurement and simplifies sample preparation before analysis, respectively.  However, ISF is difficult to obtain because its collection is limited by flow through a nanoporous extracellular matrix, and its extraction involves tissue access that generally causes bleeding. Building off our use of microneedles to create transport pathways for drug delivery into the body, we have adapted microneedles to work “in reverse” and pull material out. The combination of microneedle skin puncture followed by application of suction has enabled us to collect microliter quantities of ISF without bleeding in human subjects. ISF was found to contain almost all of the biomarkers found in companion blood samples, as well as hundreds of additional compounds not found in the blood. This technology may enable ISF to become a novel source of biomarkers for research and clinical medicine. 

Microneedle technologies are not only useful in the skin, but also for targeted drug delivery in the eye. Many drugs benefit from delivery directly to the site of their action so as to avoid side effects at off-target locations. We developed a hollow microneedle – much like a tiny hypodermic needle – that penetrates less than 1 mm into the ocular surface to reach a part of the eye called the suprachoroidal space. Injection into this space sequesters the drug in the choroid and adjacent retina, which is the site of action for most drugs given to the back of the eye. This delivery technology has been developed into a product that administers triamcinolone acetonide, which is a steroid that treats inflammation in the back of the eye. This product was approved by FDA in late 2021 and has been made available to patients since early 2022.