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Advanced therapies are commonly administered via injection even when they act within the skin tissue, and this increases the chances of off-target effects. Here we report the use of a skin patch containing a hypobaric chamber that induces skin dome formation to enable needleless delivery of advanced therapies directly into porcine, rat, and mouse skin. Finite element method modeling showed that the hypobaric chamber in the patch opened the skin appendages by 32%, thinned the skin, and compressed the appendage wall epithelia. These changes allowed direct delivery of an H1N1 vaccine antigen and a diclofenac nanotherapeutic into the skin. Fluorescence imaging and infrared mapping of the skin showed needleless delivery via the appendages. The in vivo utility of the patch was demonstrated by a superior immunoglobulin G response to the vaccine antigen in mice compared to intramuscular injection and a 70% reduction in rat paw swelling in vivo over 5 h with diclofenac without skin histology changes.
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http://dx.doi.org/10.1073/pnas.2120340119 | DOI Listing |
Wounds
August 2025
Department of Nursing, Federal University of Ceará, Ceará, Brazil.
Background: Diabetic foot ulcers (DFUs) are a major clinical challenge, particularly among patients with refractory ulcers, that often lead to severe complications such as infection, amputation, and high mortality. Innovations supported by strong clinical evidence have the potential to improve healing outcomes, enhance quality of life, and reduce the economic burden on individuals and health care systems.
Objective: To describe the design of the concurrent optical and magnetic stimulation (COMS) therapy Investigational Device Exemption (IDE) study for refractory DFUs (MAVERICKS) trial.
Fundam Clin Pharmacol
October 2025
Postgraduate Program in Pharmaceutical Science, Federal University of Juiz de Fora, Juiz de Fora, Minas Gerais, Brazil.
This review highlights the integration of drug repurposing and nanotechnology-driven delivery strategies as innovative approaches to enhance the antifungal activity of statins against mucosal candidiasis, providing a framework for future translational research and clinical application. The rising prevalence of antifungal resistance and virulence factors of Candida albicans underscore the limitations of current therapies. Statins, commonly used as lipid-lowering agents, have emerged as attractive repurposed drug candidates due to their ability to interfere with fungal ergosterol biosynthesis and Ras-mediated signaling pathways.
View Article and Find Full Text PDFStem Cell Rev Rep
September 2025
Department of Medical Genetics and Prenatal Diagnostics, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
The emergence of organoid models has significantly bridged the gap between traditional cell cultures/animal models and authentic human disease states, particularly for genetic disorders, where their inherent genetic fidelity enables more biologically relevant research directions and enhances translational validity. This review systematically analyzes established organoid models of genetic diseases across organs (e.g.
View Article and Find Full Text PDFAAPS J
September 2025
Gene Transfer and Immunogenicity Branch, Division of Gene Therapy 2, Office of Gene Therapy, Office of Therapeutic Products, Center for Biologics Evaluation and Research, US Food and Drug Administration, WO52 RM3124, 10903 New Hampshire Ave, Silver Spring, Maryland, 20993-0002, USA.
As the field of gene therapy advances and as the importance of sex as a biological variable in shaping viral immune responses is recognized, the impact of sex on adeno-associated virus (AAV) vectors mediated gene therapies remain largely unexplored. Here we review current understanding of the immune response against AAV gene therapy as well as the knowledge of sex differences observed in viral responses. We discuss sex differences in innate immune mechanisms such as Toll-like receptor recognition and complement activation, as well as the functional responses of key immune cells such as dendritic cells, macrophages, and T/B cells that are involved in AAV immunogenicity.
View Article and Find Full Text PDFClin Transl Oncol
September 2025
Department of Radiation Oncology, Vithas La Milagrosa University Hospital, Madrid, 28010, Spain.
This narrative review analyzes current evidence comparing single-session and two-session approaches in Stereotactic Body Radiation Therapy (SBRT) and high-dose-rate (HDR) brachytherapy for localized prostate cancer. These ultra-hypofractionated strategies deliver high-precision ablative doses while minimizing exposure to normal tissues. SBRT regimens with fewer than five fractions show tumor control comparable to conventional treatments, offering reduced treatment burden and increased convenience.
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