Research - Molecular Pharmaceutics and Drug Delivery

What Starts Here Changes the World

Division Research

While students choose one particular area of pharmaceutical research, they will be exposed to many other aspects of the pharmaceutical sciences in order to round out their educational experience.

Distinguished faculty in the division supervise their program of study and their research experiences.

Faculty Research Spotlight: Dr. Feng Zhang

Faculty Research Areas

Maria A. Croyle, Ph.D.

The Croyle Lab is Preparing for the Next Pandemic

Research in the Croyle Lab utilizes the principles of formulation and drug delivery with a focus on physical chemistry, structural biology, immunology and pharmacology to effectively harness viruses as vaccines and gene therapies in novel platforms allowing rapid distribution and administration to populations around the globe.  View our recent research poster to learn how we're preparing for the next pandemic.

View Poster
 

Active Research Projects in the Croyle Lab: The Anatomy of a Virus

Adenovirus graphic with illustration of dsDNA and major proteins (hexon, penton base, fiber), minor proteins (pIIIa, pVI, pVIII, pIX), and core proteins (pIVa2, pV, pVII, Mu, protease (AVP), Terminal (TP)
Adenovirus

To date, viruses have held the most promise as delivery vehicles for gene therapy because they are capable of delivering genes to certain tissues with high efficiency and establishing stable transgene expression for significant periods of time. However, routine use of viruses for therapeutic purposes is significantly limited by the innate immune response against capsid proteins, viral gene products and the therapeutic transgene.  Recombinant viral preparations must also be extremely pure for clinical use.  In this form, however, they often exhibit poor physical stability.

Research in the Croyle Lab focuses on the development of methods to reduce the immune response and associated toxicity associated with recombinant viruses and methods to evaluate the physical stability of viral vectors during processing and purification. The primary vectors under investigation are adenoviruses, adeno-associated viruses and lentiviruses.

Students in the Croyle lab are exposed to cutting edge, interdisciplinary research relevant to the fields of cell biology, virology and immunology, with basic skills in pharmaceutics and drug delivery also emphasized. Projects address basic research problems and sharpen skills in hypothesis development and open-ended problem solving. Application of research techniques to clinical settings is also emphasized.

Visit Dr. Croyle's faculty profile and the Croyle Lab site to learn more.

Zhengrong Cui, Ph.D.

The Cui group is interested in pharmaceutical formulation development, drug delivery, and tumor experimental therapy. Below are two representative projects:

Engineering and characterization of dry powders of biologics and nucleic acid-based products. We apply thin-film freeze-drying technology to prepare dry powders of peptides, monoclonal antibodies (mAbs), messenger RNA-lipid nanoparticles (mRNA-LNPs), small interfering RNA (siRNA), antisense oligos (ASOs), plasmid DNA, various types of vaccines, as well as live organisms (e.g., viruses, bacteria, and bacteriophages). The dry powders increase the thermostability of the products. They can be reconstituted for injection or used directly for efficient pulmonary or intranasal delivery due to their unique aerosol properties.

Synthesis and evaluation of antitumor compounds: We synthesize immunogenic cell death inducers. For example, we have synthesized 4-(N)-docosahexaenoyl 2’,2’-difluorodeoxycytidine (DHA-dFdC), a compound with potent, broad spectrum antitumor activity. Recent data confirmed that the compound is a bona fide immunogenic cell death (ICD) inducer. We are elucidating the mechanism underlying the ICD-inducing activity of the compound and applying the compound to sensitize immunologically ‘cold’ tumors to immunotherapy.

More peer-reviewed publications can be found at https://pubmed.ncbi.nlm.nih.gov/?term=zhengrong+cui&sort=date

Visit Dr. Cui's faculty profile page to learn more.

Debadyuti (Rana) Ghosh, Ph.D.

Ghosh Lab Research Interests

Work in Dr. Ghosh’s lab focuses on biologically-inspired, rational design of biomolecules (i.e. peptides and proteins) and nanoscale materials for therapeutics in cancer and mucosal-associated diseases.

One area of emphasis is the use of combinatorial libraries to identify peptides that achieve transport through biological barriers, including the blood-brain barrier, mucus, and in solid tumors.

From this information, design criteria can be developed towards the design of drug carriers that achieve improved, therapeutic delivery.

Another long-term goal of the lab is to exploit the biology of diseases to develop biological nanoparticles that achieve successful delivery of therapeutic agents.

Visit Dr. Ghosh's faculty profile and the Ghosh Lab site to learn more.

Hugh D. Smyth, Ph.D.

Research

Dr. Smyth’s group focuses on Drug Delivery, Formulation Science, and Pharmaceutical Engineering. Work in Dr. Smyth’s lab focuses on the development of novel methods for drug delivery including inhalation, nasal, transdermal, ophthalmic, and oral delivery systems for a variety of diseases. Translation of these technologies to the clinic is the long-term goal of the lab and is supported by developing a mechanistic understanding of the complex physical and biological systems.

Visit Dr. Smyth's faculty profile and the Smyth Lab site to learn more.

Janet C. Walkow, Ph.D.

Janet joined The University of Texas  in 2008, building on a successful pharmaceutical industry career, heading efforts ranging from R&D and Human Resources to Global Corporate Strategy. Leading the Innovating for Health (i4Health) Institute (formerly the Drug Dynamics Institute), Janet brings novel approaches and solutions that promote development of health technologies, facilitate bioscience startups, and cultivate interdisciplinary technology readiness, and she has been named a University of Texas gamechanger.

Janet is known in academic circles for developing cutting-edge ways and engaging educational tools. Her successful edX MOOC, Take Your Medicine, has enrolled tens of thousands of students, who explore how new drug therapies are developed. Her successful Innovating for Health program – recently approved as a certificate program -  empowers students to be dynamic thinkers who are  impacting the health innovation landscape. She was named a University Fellow of the OpEd Project in 2021.

A leader in efforts to empower entrepreneurs and women, Janet’s involvement spans numerous local and global innovation efforts including the Texas Global Health Security, Same Sky, Texas Venture Mentoring Services, and numerous academic, nonprofit, and corporate initiatives. As a Public Voices Fellow and Ambassador for the OpEd Project, Janet gives voice to issues regarding health, education, and women. Her recent Board service includes the Ann Richards School for Young Women Leaders Foundation (Past Chair), the Health Promotion Council, Women in Neuroscience, and Harvard Kennedy School Women’s Leadership Board.

Visit Dr. Walkow's faculty profile and the Innovating for Health (i4Health) Institute site to learn more.

Robert O. (Bill) Williams III, Ph.D.

The Williams Lab:
The research in my laboratory focuses on the formulation development, optimization, and delivery of low molecular weight drugs, peptides, and proteins by a variety of technologies, including depot drug delivery, oral drug delivery and pulmonary/nasal/ophthalmic drug delivery.  Significant effort is devoted to research to enhance drug solubility and dissolution through novel particle engineering technologies, including thin film freezing and precipitation processes, and thermal processes such as hot melt extrusion. My lab has also applied particle engineering techniques to delivery of biologics (e.g., monoclonal antibodies, mRNA/LNPs, DNA).

In addition, other current research has focused on aerosol device technology, and analytical methods to quantitate and characterize these technologies. Analytical techniques including cascade impaction, HPLC, GC, X-ray diffraction, scanning electron microscopy, atomic force microscopy, Karl Fisher, laser light diffraction and TLC are routinely used to investigate raw materials and formulations.


Publications:
Please click on the following links to see the most recent papers published from the Williams’ group:


Lab Members:
Visit the Lab Members tab of my faculty profile for additional information.

Feng Zhang, Ph.D.

Research Interests

Implants and Medical Devices for Long-acting Drug Delivery
Patient adherence to drug therapies remains a major obstacle to realizing the full therapeutic benefit of drug treatments in the real world. Depending on the polymers used to modulate drug release, implants can be categorized as biodegradable or removable implants.

Implants may be designed as a matrix composed of drug and polymer, wherein the release behavior is driven by a pore network created by the distribution of drug in the polymer. In such a system, the drug release rate is strongly dependent on drug loading, degradation rate of polymeric matrix, and the implant geometry. Alternatively, implants can be designed as reservoir systems, wherein a core of drug and polymer is surrounded by a rate-controlling polymer membrane. Since the drug release kinetics from reservoir implants are limited by diffusion through the rate-controlling membrane, they are capable of decoupling the treatment duration of a single implant from its release rate.

My lab is investigating the correlation between process, composition and quality attributes of the following types of implants.

  • Thermoplastic poly(urethane) and ethylene vinyl-acetate based biodurable implants prepared using melt extrusion process
  • Poly(lactide-co-glycolide) based biodegradable implants prepared using melt extrusion process

Continuous Granulation to Improve Powder Properties
There is increasing interest in the pharmaceutical industry to implement continuous manufacturing processes for pharmaceutical manufacturing. Continuous manufacturing offers several advantages such as flexible operation, lower operational cost, and improved product quality. Continuous manufacturing also enables the processing of pharmaceutical formulation at “extreme conditions” (i.e. higher temperature and higher pressure) that are not feasible in the conventional batch processes.

Roller compaction (RC) has been implemented in continuous manufacturing to improve the flow properties of blends for most of tablet manufacturing. However, twin-screw based melt granulation (TSMG) and wet granulation (TSWG) are expected, in many ways, to be a better alternative to RC because of the unique mechanisms for granule formation during twin-screw granulation, and the modular design of twin-screw extruders. Thus, one goal of this project is to assess the advantages and limitations of the continuous TSMG and TSWG processes in comparison to RC, which is the leading continuous tablet manufacturing process.

Our research efforts are concentrated on:

  • Developing a mechanistic understanding of the thermal and mechanical stresses imposed on formulation during TSMG and TSWG.
  • Developing formulation and processing strategies to enable TSMG and TSWG, including thermal binder selection and thermal stress reduction.
  • Investigating the effect of the formulation composition and processing parameters on the critical quality attributes of granules and final tablets prepared with TSMG and TSWG.
  • Simulating and modeling of TSMG and TSWG processes.

Formulation and Processing Strategies for Bioavailability Enhancement
Especially drugs for virology and oncology treatment, about 70% of drug candidates in the development pipeline face the challenges of the solubility-limited absorption. The number is expected to rise even further. Formulation scientists are increasingly relying on solubilization technologies, including amorphous drug substance, nanocrystals, lipids, and amorphous solid dispersions (ADS), to achieve enhanced and more consistent bioavailability of these drugs.

Amorphous solid dispersions (ASDs) are polymeric matrices containing molecularly dispersed drugs. ASD technology is becoming the preferred drug delivery methodology to enhance the bioavailability of drugs with solubility-limited absorption. Improved bioavailability is attributed to the high transient solubility of the amorphous drug in the gastrointestinal tract as the result of the formation of amorphous nanoparticles in situ. Despite all of the success, more research on ASD technology is needed. The effect of formulation composition and manufacturing process on the performance of ASDs needs to be understood better, and novel analytical methods need to be developed to assess in vivo performance of ASDs. Without this knowledge, the formulation composition and manufacturing process could not be rationally designed, the quality of products cannot be ensured, and patients’ health and safety are ultimately at risk.

My group’s research interest in ASDs includes:

  • Studying molecular-level drug-excipient and excipient-excipient interactions, and to investigate the impact of these interactions on the properties of ASDs.
  • Developing advanced analytical methods to characterize behaviors of ASDs in solution state.
  • Understanding the effect of manufacturing processes on the physical stability in solid-state, and supersaturation/speciation in solution-state.

Visit Dr. Zhang's faculty profile page to learn more.

Virtual Lab Tours

Ghosh Lab

Williams/Zhang Lab