Maria Vitoria Bentley - Full Professor at the School of Pharmaceutical Sciences of Ribeirão Preto, USP
Maria Vitoria Bentley - Full Professor at the School of Pharmaceutical Sciences of Ribeirão Preto, USP
Biography
I hold a degree in Pharmacy from the University of São Paulo (USP), where I also completed my PhD in Pharmaceutical Technology. I pursued postdoctoral training at the University of Manchester, UK. I joined USP as an Assistant Professor and advanced through all stages of the academic career. Since 2006, I have served as a Full Professor at the School of Pharmaceutical Sciences of Ribeirão Preto, USP. I have published over 139 peer-reviewed articles and hold an H-index of 45. I have filed five patents in the field of nanotechnology. I coordinate the NanoGeneSkin Laboratory, which focuses on drug delivery to and through the skin, antisense therapy for skin diseases, and pharmaceutical nanotechnology. I actively participate in international committees, including the Executive Committee of the Globalization of Pharmaceutical Education Network (GPEN, USA). My work has been recognized with several awards, including the CAPES Thesis Award in the Pharmacy category (2006), Second Place in the Natura Campus Innovation Award (2010), the Best Abstract Award at the 2023 Annual Meeting of the American Association of Pharmaceutical Scientists (AAPS), and the Most Cited Paper 2005 Award from Elsevier –European Journal of Pharmaceutics and Biopharmaceutics, among others. I have supervised dozens of PhD students and postdoctoral fellows. I have also played a prominent role in university administration, having served as Vice Provost for Undergraduate Studies at USP and as Director of the School of Pharmaceutical Sciences of Ribeirão Preto. Additionally, I have contributed to Brazil’s research funding system as a member and coordinator of scientific advisory boards at the National Council for Scientific and Technological Development (CNPq) and the São Paulo Research Foundation (FAPESP).
Interview
NanoSphere: Tell us a bit about yourself—your background, journey, and what led you to where you are today.
Maria Vitoria: My background in pharmacy has shaped my scientific career toward addressing formulation challenges to optimize drug delivery into and across the skin—an area that became the focus of my PhD research. At the time, this approach was still relatively unknown in Brazil, and my work was pioneering in developing dermatological formulations using skin penetration enhancers and in vitro permeation testing in animal skin models. Motivated to better understand the influence of such molecules on the skin barrier function, I pursued a postdoctoral fellowship at the University of Manchester, where I conducted physicochemical, spectroscopic, and microscopic studies of the stratum corneum, focusing on the effects of both lipophilic and hydrophilic permeation enhancers.
With the advancement of nanotechnology and nanomedicine worldwide, I initiated research on a particular type of lipid nanoparticle based on reverse mesophase liquid crystal systems. To this day, this remains the most extensively studied nanocarrier in our research group for the skin delivery of various drugs, including in applications such as photodynamic therapy and antisense therapy using siRNA for skin diseases.
My research has increasingly focused on the development of innovative therapeutic solutions based on nanotechnology for the topical and targeted delivery of both conventional drugs and nucleic acids, such as siRNA and antisense oligonucleotides. Our goal is to develop safer and more effective treatments for complex skin disorders. I highlight here the pioneering nature of our work on topical siRNA therapy for treating genetically based skin diseases, both in Brazil and internationally.
Skin diseases such as psoriasis, skin cancer, and vitiligo represent major global public health challenges due to their high prevalence, clinical complexity, and profound psychosocial impact. Melanoma, for example, is associated with a high mortality rate when not detected early. Psoriasis is linked to systemic inflammatory comorbidities, while vitiligo, though not life-threatening, leads to social stigma and exclusion. In this context, our work with nanostructured delivery platforms offers several advantages, such as active compound protection, enhanced skin penetration, controlled release, and reduced adverse effects, positioning them as promising strategies for the effective and safe treatment of complex dermatological conditions.
Our research follows a strongly translational approach, bridging fundamental science and real-world clinical application. It contributes to therapeutic innovation, the advancement of personalized medicine, and the improvement of patients' quality of life. This trajectory represents a strategic scientific contribution with high potential impact in both pharmaceutical technology and the transformation of health outcomes for affected populations.
One of the major milestones of my career has been the coordination of the National Institute of Science and Technology in Pharmaceutical Nanotechnology (INCT-NANOFARMA), which brings together dozens of research institutions across Brazil and several eminent international collaborators from prestigious universities such as Harvard University, Monash University, Harvard School of Engineering and Applied Sciences, Harvard Medical School, Georgia Institute of Technology, University College Dublin, Ludwig-Maximilians-Universität München, the University of British Columbia, the University of Porto, among others. Through INCT-NANOFARMA, we have advanced cutting-edge research in nanotechnology for therapeutic applications across multiple diseases—including gene therapy based on mRNA, enzyme replacement therapy, and drug-siRNA co-delivery systems. Our mission is to translate basic science into clinical solutions, fostering therapeutic innovation, personalized medicine, and improved quality of life. This represents a strategic scientific contribution with societal, technological, and public health impact.
Key genes implicated in skin diseases can be selectively silenced for therapeutic benefit. RNA interference (RNAi), a natural cellular mechanism activated by double-stranded RNA, downregulates the expression of specific protein-coding genes. RNAi has become a foundational strategy in antisense gene therapy, achieved through the delivery of synthetic small RNAs or the endogenous expression of shRNA, siRNA, and miRNA.
To illustrate the alignment of our research with transformative discoveries in gene therapy, we refer to key Nobel Prizes: ·
🟣 2006 – Nobel Prize awarded for the discovery of RNAi using siRNA, enabling gene-silencing approaches.
☑️ 2007 – Our group began studying topical siRNA-based antisense therapy for skin diseases.
🟣 2009 – Nobel recognition of ribosome structure and function, deepening understanding of protein biosynthesis.
🟣 2015 – Nobel awarded for insights into DNA repair mechanisms.
🟣 2020 – Breakthrough in CRISPR-Cas gene editing recognized.
☑️ 2021 – Our research initiated on lipid nanoparticles (LNPs) for mRNA-based gene vaccines.
🟣 2023 – Nobel Prize awarded for mRNA vaccine and RNA-based therapies.
☑️ 2023 – In parallel, our group launched studies on LNPs for microRNA delivery in the treatment of skin diseases.
🟣 2024 – Nobel recognition for pioneering work on microRNA and its role in gene regulation.
siRNA has emerged as a powerful and widely used tool due to its high potency and selectivity. By enabling precise silencing of disease-driving genes, it holds tremendous promise for treating conditions with well-defined molecular targets. Topical siRNA delivery, in particular, provides a unique opportunity to locally modulate gene expression and treat skin diseases while avoiding systemic side effects. Despite its therapeutic advantages, topical siRNA delivery faces significant challenges:
- Limited skin penetration due to the robust skin barrier;
- Rapid degradation by endogenous enzymes;
- Negative charge hindering membrane permeability;
- Inefficient cellular uptake.
We are currently engaged in exciting projects focused on identifying gene-silencing targets involved in skin diseases, encompassing the various stages of the pathological processes that lead to gene upregulation. This work involves a systematic investigation of microRNAs and siRNAs. The findings will support the development of effective RNAi-based strategies using lipid nanoparticles (LNPs), aiming to tailor therapeutic approaches to the specific stages of chronic inflammatory skin diseases.
NanoSphere: Given the formidable barrier posed by the stratum corneum and the intracellular environment, what do you see as the most promising strategy—nanoparticle-based or physical—for achieving efficient topical delivery of siRNA in dermatological applications, and why?
Maria Vitoria: To enhance the delivery of siRNA, one effective strategy is to load it into lipid nanoparticles. siRNA is inherently a negatively charged molecule at physiological pH, which makes it difficult to penetrate cell membranes. To overcome this challenge, siRNA can be complexed with cationic lipids or polymers. Ionizable lipids are important for the incorporation of siENA into the lipid nanoparticle and to provide effective endosomal escape.One of the most promising approaches involves lipid nanoparticles, which include both liquid crystalline nanoparticles and nano-structured lipid carriers. These nanoparticles provide a versatile and efficient platform for siRNA delivery, especially when targeting specific tissues like the skin. Their structure allows for both protection of the siRNA and enhanced cell uptake. In addition to the lipid nanoparticles themselves, skin penetration enhancers added to nanoparticle composition play a critical role. These enhancers help overcome the skin’s natural barrier, allowing the siRNA-loaded nanoparticles to penetrate more effectively, ensuring that the therapeutic agent reaches its target. However, the combination of lipid nanoparticles containing absorption-promoting lipids with physical methods (iontophoresis and microneedles) can further optimize siRNA penetration into the epidermis. Also, understanding the molecular targets involved in skin diseases is important for the success of this therapeutic approach.
NanoSphere: If there’s one key message or insight you’d like to share with readers about the future of nanomedicine, what would it be?
Maria Vitoria: The future of nanomedicine for inflammatory skin diseases lies in the precise, safe, and minimally invasive interventions to deliver gene-silencing agents such as siRNA and other RNAi. Lipid-based nanoparticles represent a promising platform to enhance siRNA stability and enable its penetration into the viable epidermis, allowing for targeted modulation of key inflammatory pathways. By combining intelligent nanocarrier design with deep molecular insights into disease pathogenesis, we are advancing toward topical therapies that are not only more effective but also tailored and safer. The integration of nanotechnology with omics data, artificial intelligence, and real-time imaging technologies is set to transform this field, ushering in a new era of personalized and responsive treatments for chronic inflammatory skin conditions.
Maria Vitoria: The future of nanomedicine for inflammatory skin diseases lies in the precise, safe, and minimally invasive interventions to deliver gene-silencing agents such as siRNA and other RNAi. Lipid-based nanoparticles represent a promising platform to enhance siRNA stability and enable its penetration into the viable epidermis, allowing for targeted modulation of key inflammatory pathways. By combining intelligent nanocarrier design with deep molecular insights into disease pathogenesis, we are advancing toward topical therapies that are not only more effective but also tailored and safer. The integration of nanotechnology with omics data, artificial intelligence, and real-time imaging technologies is set to transform this field, ushering in a new era of personalized and responsive treatments for chronic inflammatory skin conditions.