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Mon Oct 23 08:02:45 PDT 2023
Medgadget (Medical Technology) Daily Digest (Unofficial)
(https://www.medgadget.com/2023/10/suction-cup-delivers-drugs-through-cheek.html) Suction Cup Delivers Drugs Through Cheek
Oct 23rd 2023, 09:54
Researchers at ETH Zurich in Switzerland have developed an alternative to injections as a way to deliver large drugs, such as peptides, minimally invasively into the blood stream. The suction cup created by these researchers is inspired by octopus suckers, and it affixes to the mucosal lining of the inside of the cheek. The cup stays in place because a vacuum is drawn when the patient presses it onto their cheek lining. This vacuum helps to stretch the tissue, making it more permeable to drugs. The suction cup also exposes the mucosal lining to an additional reagent called a permeability enhancer, which fluidizes the cell membranes of the mucosa, allowing peptides to traverse the lining more easily. In tests so far, the suction cups have produced successful delivery of medication to the blood stream, and have been described by volunteers as preferable to injections.
No one enjoys injections, but for some people they are a source of terror. This is more common with children, but many adults also have a fear of needles. Moreover, for people who need to take a drug regularly, getting repeat injections is no fun, with repeated trauma at the injection sites. However, there is often no easy replacement for injections, particularly for drugs that are not usually suitable for oral, inhalational ,or transdermal administration, such as peptides.
This latest invention is an attempt to deliver such drugs in a minimally invasive fashion, through the inside wall of the cheek. The concept was born when one of the researchers noticed a half peppercorn stuck to the inside of his cheek during a meal, which resonated with him as a way to affix a drug-filled container to the slippery oral mucosa. However, the oral mucosa itself is not particularly amenable to drug delivery, with its dense nature providing a barrier.
To circumvent this, the researchers combined the suction effect of the cup, which stretches the tissue somewhat, potentially increasing its permeability, with an additional substance called a permeability enhancer that makes the treated cell membranes more permeable. This combination resulted in the successful delivery of drugs through mucosa.
However, the technology did require some fine-tuning, which the researchers performed using a post-mortem pig mucosa as a testing bed. “We had to find out what geometry and how much of a vacuum were required to hold the suction cup in place on the mucosal lining of the cheek and to stretch it sufficiently without causing any damage,” said Klein Cerrejon, a researcher involved in the study.
Study in journal Science Translational Medicine: (https://www.science.org/doi/10.1126/scitranslmed.abq1887) Boosting systemic absorption of peptides with a bioinspired buccal-stretching patch
Via: (https://ethz.ch/en/news-and-events/eth-news/news/2023/09/how-a-suction-cup-delivers-medications-to-the-bloodstream.html) ETH Zurich
(https://www.medgadget.com/2023/10/enhanced-mrna-vaccine-may-work-intranasally.html) Enhanced mRNA Vaccine May Work Intranasally.
Oct 23rd 2023, 09:37
Researchers at MIT have developed an enhanced mRNA vaccine system that can elicit a greater immune response at lower doses. The vaccine technology is so potent that it may be useful for intranasal COVID-19 vaccines. This would have the benefit of localized immunity in the nasal mucus membranes that could kill the SARS-CoV-2 virus before it enters the body. The system includes an mRNA strand that encodes the viral spike protein, as with earlier generations of such vaccines, but in this case the strand also encodes for an immune protein called C3d. This protein typically binds to antigens, such as the spike protein, in the body and amplifies the antibody response against them. The mRNA strand included in the vaccine encodes the spike protein already fused with C3d, ensuring a potent immune response.
mRNA vaccines have opened new possibilities in preventing severe disease, which was particularly useful during the recent COVID-19 pandemic. However, these vaccines are still very new, and there is room for improvement. For instance, increasing the immune responses elicited by such vaccines could lead to greater and longer protection from disease, and may also reduce the dose required, which would reduce the cost of treatment and increase access to vaccines in low resource regions. Moreover, a highly potent vaccine may be suitable for intranasal administration.
Not only is this less invasive than injections, and therefore more suitable for children and other nervous patients, but can also lead to strong immunity in the nasal membranes. “With intranasal vaccination, you might be able to kill Covid at the mucus membrane, before it gets into your body,” said Daniel Anderson, a researcher involved in the study. “Intranasal vaccines may also be easier to administer to many people, since they don’t require an injection.”
Traditional mRNA vaccines consist of a lipid nanoparticle enclosing a strand of mRNA that encodes an antigen protein, which in this case is the viral spike protein. The researchers took this one step further, designing the mRNA strand to encode the spike protein fused to C3d, which greatly enhances its stimulatory properties for the immune system, and specifically increases the antibody response. However, the researchers also focused on the lipid composition within the nanoparticle delivery vehicle, as certain lipids can help to enhance immune responses.
“We understood that nanoparticles themselves could be immunostimulatory, but we weren’t quite sure what the chemistry was that was needed to optimize that response,” said Anderson. “So instead of trying to make the perfect one, we made a library and evaluated them, and through that we identified some chemistries that seemed to improve their response.”
Study in journal Nature Biomedical Engineering: (https://www.nature.com/articles/s41551-023-01082-6) Enhancing the immunogenicity of lipid-nanoparticle mRNA vaccines by adjuvanting the ionizable lipid and the mRNA
Via: (https://news.mit.edu/2023/mit-engineers-design-more-powerful-rna-vaccines-0907) MIT
Michael Reeder LCPC
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