About

Maria A. Croyle, Ph.D., is a Professor of Molecular Pharmaceutics and Drug Delivery at the University of Texas at Austin, holding the Glaxo Wellcome Professorship. Her research focuses on the development of methods to reduce the immune response and associated toxicity caused by recombinant viruses, as well as evaluating the physical stability of viral vectors during processing and purification. The primary vectors under investigation in her lab include adenoviruses, adeno-associated viruses, and lentiviruses. Her work aims to improve the efficacy and safety of viral vectors used in gene therapy, addressing challenges related to immune responses, viral stability, and clinical application. Her research integrates interdisciplinary approaches spanning cell biology, virology, immunology, pharmaceutics, and drug delivery. Students in her lab engage in projects that address basic research problems, develop hypothesis-driven solutions, and apply research techniques to clinical settings. Dr. Croyle's contributions advance the understanding of viral vector development for therapeutic purposes, with an emphasis on improving gene delivery systems and their translational potential.

Research topics

• Biology
• Materials science
• Virology
• Medicine
• Pharmacology
• Nanotechnology
• Immunology
• Composite material
• Bioinformatics
• Biochemistry
• Chemistry
• Biotechnology

Selected publications

• Assessment of <i>In Vitro</i> Models of the Human Buccal Mucosa for Vaccine and Adjuvant Development

  Molecular Pharmaceutics · 2025-03-26 · 1 citations

  articleOpen accessSenior authorCorresponding

  To understand requirements for immunization via the oral mucosa, an in vitro model that recapitulates the physical barrier of the mouth, allows for quantification of antigen uptake and permeability and mounts an inflammatory response to antigen and adjuvant is needed. The physical structure of 4 models of the human oral mucosa was determined by histochemical staining and transepithelial electrical resistance (TEER) measurements. A TR146 based air–liquid interface (ALI) model most closely mimicked in vivo conditions. This was confirmed by validation studies using dextran and caffeine as diffusant molecules. Apparent permeability coefficients (Papp) of adenovirus (Ad) and adeno-associated virus (AAV) in this model were 4.3 × 10–13 and 2.2 × 10–10 respectively, while 100% of the total dose of H1N1 influenza remained in the epithelial layer. Sodium glycocholate and a hyperosmotic formulation improved the amount of Ad (p = 0.02) and AAV (p = 0.003) that entered the epithelium, respectively. Significant amounts of IL-6 (45.1 pg/mL), GM-CSF (94.7 pg/mL) and IFN-γ (4.3 pg/mL) were produced in response to influenza infection. Treatment with an AS03-like adjuvant induced production of IL-6 (34.9 pg/mL), TNF-∝ (43 pg/mL), GM-CSF (121.2 pg/mL) and IFN-γ (14.1 pg/mL). This highlights the contribution of differentiated epithelial cells to the immune response to vaccines and adjuvants.

  PublisherOA PDFDOI

• Composition, stabilization and delivery of virus-based vaccines: considerations to break free of the cold chain

  Advanced Drug Delivery Reviews · 2025-10-15 · 1 citations

  reviewSenior author
  PublisherDOI

• Identification of film-based formulations that move mRNA lipid nanoparticles out of the freezer

  Molecular Therapy — Nucleic Acids · 2024-03-26 · 12 citations

  articleOpen accessSenior author

  COVID-19 vaccines consisting of mRNA lipid nanoparticles (LNPs) encoding the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein antigen protected millions of people from severe disease; however, they must be stored frozen prior to use. The objective of this study was to evaluate the compatibility and stability of mRNA LNPs within a polymer-based film matrix. An optimized formulation of polymer base, glycerol, surfactants, and PEGylated lipid that prevents damage to the LNP due to physical changes during the film-forming process (osmotic stress, surface tension, spatial stress, and water loss) was identified. Surfactants added to LNP stock prior to mixing with other film components contributed to this effect. Formulations prepared at pH ≥ 8.5 extended transfection efficiency beyond 4 weeks at 4°C when combined with known nucleic acid stabilizers. mRNA LNPs were most stable in films when manufactured in an environment of ∼50% relative humidity. The optimized formulation offers 16-week stability at 4°C.

  PublisherOA PDFDOI

• Physical characteristics and stability profile of recombinant plasmid DNA within a film matrix

  European Journal of Pharmaceutics and Biopharmaceutics · 2023-08-09 · 5 citations

  articleSenior authorCorresponding
  PublisherDOI

• COVID-19 Vaccines and the Virus: Impact on Drug Metabolism and Pharmacokinetics

  UNC Libraries · 2023-10-24

  articleOpen accessSenior author

  This article reports on an American Society of Pharmacology and Therapeutics, Division of Drug Metabolism and Disposition symposium held at Experimental Biology on April 2nd, 2022, in Philadelphia. As of July 2022, over 500 million people have been infected with SARS-CoV-2 (the virus causing COVID-19) and over 12,000,000,000 vaccine doses have been administered. Clinically significant interactions between viral infections and hepatic drug metabolism were first recognized over 40 years ago during a cluster of pediatric theophylline toxicity cases attributed to reduced hepatic drug metabolism amidst an influenza B outbreak. Today, a substantive body of research supports that the activated innate immune response generally decreases hepatic cytochrome P450 (CYP) activity. The interactions extend to drug transporters and other organs and have the potential to impact drug absorption, distribution, metabolism, and excretion (ADME). Based on this knowledge, altered ADME is predicted with SARS-CoV-2 infection or vaccination. The report begins with a clinical case exploring the possibility of SARS-CoV-2 vaccination increasing clozapine levels. This is followed by discussions of how SARS-CoV-2 infection or vaccines alter the metabolism and disposition of complex drugs, such as nanoparticles and biologics and small molecule therapies. The review concludes with a discussion of the effects of viral infections on placental amino acid transport and their potential to impact fetal development. The session improved our understanding of the impact of emerging viral infections and vaccine technologies on drug metabolism and disposition, which will help mitigate drug toxicity and improve drug and vaccine safety and effectiveness. Significance Statement Altered pharmacokinetics of small molecule and complex molecule drugs and fetal brain distribution of amino acids following SARS-CoV-2 infection or immunization are possible. The proposed mechanisms involve decreased liver CYP metabolism of small molecules, enhanced innate immune system metabolism of complex molecules and altered placental and fetal blood-brain barrier amino acid transport, respectively. Future research is needed to understand the effects of these interactions on adverse drug responses, drug and vaccine safety and effectiveness and fetal neurodevelopment.

  PublisherDOI

• Challenges in vaccine transport: can we deliver without the cold chain?

  Expert Review of Vaccines · 2023-10-20 · 12 citations

  editorialOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

• COVID-19 Vaccines and the Virus: Impact on Drug Metabolism and Pharmacokinetics

  Drug Metabolism and Disposition · 2022 · 20 citations

  • Pharmacology
  • Medicine
  • Biology
  PublisherOA PDFDOI

• Thermostability and in vivo performance of AAV9 in a film matrix

  Communications Medicine · 2022 · 14 citations

  Senior authorCorresponding
  • Materials science
  • Chemistry
  • Biology

  BACKGROUND: Adeno-associated virus (AAV) vectors are stored and shipped frozen which poses logistic and economic barriers for global access to these therapeutics. To address this issue, we developed a method to stabilize AAV serotype 9 (AAV9) in a film matrix that can be stored at ambient temperature and administered by systemic injection. METHODS: AAV9 expressing the luciferase transgene was mixed with formulations, poured into molds and films dried under aseptic conditions. Films were packaged in individual particle-free bags with foil overlays and stored at various temperatures under controlled humidity. Recovery of AAV9 from films was determined by serial dilution of rehydrated film in media and infection of HeLa RC32 cells. Luciferase expression was compared to that of films rehydrated immediately after drying. Biodistribution of vector was determined by in vivo imaging and quantitative real-time PCR. Residual moisture in films was determined by Karl Fischer titration. RESULTS: AAV9 embedded within a film matrix and stored at 4 °C for 5 months retained 100% of initial titer. High and low viscosity formulations maintained 90 and 85% of initial titer after 6 months at 25 °C respectively. AAV was not detected after 4 months in a Standard Control Formulation under the same conditions. Biodistribution and transgene expression of AAV stored in film at 25 or 4 °C were as robust as vector stored at -80 °C in a Standard Control Formulation. CONCLUSIONS: These results suggest that storage of AAV in a film matrix facilitates easy transport of vector to remote sites without compromising in vivo performance.

  PublisherOA PDFDOI

• Evaluation of intermolecular interactions required for thermostability of a recombinant adenovirus within a film matrix

  Journal of Controlled Release · 2021-11-12 · 13 citations

  articleSenior authorCorresponding
  PublisherDOI

• Immunization and Drug Metabolizing Enzymes: Focus on Hepatic Cytochrome P450 3A

  Expert Review of Vaccines · 2021-03-05 · 8 citations

  articleOpen accessSenior authorCorresponding

  Objective Infectious disease emergencies like the 2013–2016 Ebola epidemic and the 2009 influenza and current SARS-CoV-2 pandemics illustrate that vaccines are now given to diverse populations with preexisting pathologies requiring pharmacological management. Many natural biomolecules (steroid hormones, fatty acids, vitamins) and ~60% of prescribed medications are processed by hepatic cytochrome P450 (CYP) 3A4. The objective of this work was to determine the impact of infection and vaccines on drug metabolism.Methods The impact of an adenovirus-based vaccine expressing Ebola glycoprotein (AdEBO) and H1N1 and H3N2 influenza viruses on hepatic CYP 3A4 and associated nuclear receptors was evaluated in human hepatocytes (HC-04 cells) and in mice.Results CYP3A activity was suppressed by 55% in mice 24 h after administration of mouse-adapted H1N1, while ˂10% activity remained in HC-04 cells after infection with H1N1 and H3N2 due to global suppression of cellular translation capacity, indicated by reduction (70%, H1N1, 56%, H3N2) of phosphorylated eukaryotic translation initiation factor 4e (eIF4E). AdEBO suppressed CYP3A activity in vivo (44%) and in vitro (26%) 24 hours after infection.Conclusion As the clinical evaluation of vaccines for SARS-CoV-2 and other global pathogens rise, studies to evaluate the impact of new vaccines and emerging pathogens on CYP3A4 and other metabolic enzymes are warranted to avoid therapeutic failures that could further compromise the public health during infectious disease emergencies.

  PublisherOA PDFDOI

Recent grants

• NIH Grant U01AI078045

  NIH · $2.5M · 2015

• NIH Grant R21GM069870

  NIH · $216k · 2006

Frequent coauthors

• William C. Zamboni

  UNC Lineberger Comprehensive Cancer Center

  66 shared

• William G. Honer

  University of British Columbia

  65 shared

• Eliza R. McColl

  University of Toronto

  65 shared

• Mark T. Heise

  65 shared

• Kerry B. Goralski

  Izaak Walton Killam Health Centre

  65 shared

• Micheline Piquette‐Miller

  University of Toronto

  65 shared

• James M. Wilson

  22 shared

• Gary Wong

  Academy of Medical Sciences

  21 shared

Education

• PhD, Pharmaceutics

  Univerfsity of Michigan

  1997

• BS, Pharmacy

  University of Pittsburgh

  1992