期刊
出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2120340119
关键词
needleless delivery; advanced therapeutics; skin; drug delivery; vaccine
资金
- Biotechnology and Biological Sciences Research Council PhD CASE studentship
- Engineering and Physical Sciences Research Council (EPSRC) [EP/S021167/1]
- RoseTree's Trust
- StonyGate Trust
- EPSRC [EP/S021159/1]
This study demonstrates a novel method for needleless delivery of advanced therapies using a skin patch. By opening the skin appendages with a hypobaric chamber, direct delivery of vaccine antigens and drug nanoparticles was achieved. The patch was shown to enhance immune response to vaccine antigens and effectively reduce rat paw swelling.
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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