Melanoma is a deadly form of skin cancer that has been on the increase in the US for 30 years. Almost 1
Researchers will present their findings today at the National Meeting and Exposition of the American Chemical Society (ACS) in the fall of 2019.
"Our patch has a unique chemical coating and action that allows it to be applied to and removed from the skin in just one minute, while still delivering a therapeutic dose of medication," says Yanpu He , a doctoral student who has been involved in the development of the device. "Our plasters induce a robust antibody response in living mice and are promising in triggering a strong immune response in human skin."
Topical ointments can be used to administer medication to the skin, but they can only penetrate it at close range. Although syringes are an effective drug delivery mode, they can be painful. Syringes can also be uncomfortable for patients and lead to irregularities.
Micro-needle patches made with a layer-by-layer (LbL) method are a simple and painless way to perform the treatment. Using the LbL method, researchers coat a surface with molecules of alternating positive and negative charges. In order for a sturdy drug film to form on the surface of the patch, each adjacent layer must be strongly attracted to each other and also by the microneedle. "But this attraction makes the entire movie very 'sticky'," he notes. "Previous methods that have retained this" sticky "nature may take up to 90 minutes for a sufficient amount of the drug to escape from the patch and get into the skin."
Paula T. Hammond, Ph.D., along with her PhD students He, Celestine Hong and other colleagues from the Massachusetts Institute of Technology (MIT) have found a way around this problem. They developed a new pH-responsive polymer with two parts. "The first part contains amine groups that are positively charged at the pH at which we make the microneedles but become neutral at the pH of the skin," he says. "The second part contains non-charged carboxylic acid groups when the microneedles are made, but they charge negatively when the patch is applied to the skin, causing the overall charge to change from positive to negative." While sticky negative-positive-negative layers are still required to make LbL films, when applied to the skin, the team quickly switches to backing negative-negative-negative layers. After the microneedles pierce the skin and implant the LbL drug film under the skin, the drug leaves the patch quickly.
Using chicken ovalbumin as a model antigen, the team inoculated mice with their patches and compared the results with intramuscular and subcutaneous injections. The microneedle treatment produced nine times the antibody level compared to intramuscular injections (eg, for flu shots) and 160 times the antibody level compared to subcutaneous injections (eg, measles vaccines). They also saw effective immune activation in human skin surgical specimens.
"Our patch technology could be used to deliver vaccines against various infectious diseases," says Hammond. "We are pleased, however, with the possibility that the patch is another tool in the arsenal of cancer oncologists, especially against melanoma."
To create a melanoma vaccine, the researchers developed an antigen that contains a marker that is often overexpressed by melanoma cells. and an adjuvant which produces a general danger signal to the immune system and enhances its response. They then tested various LbL microneedle film assemblies of antigen and adjuvant in immune cells derived from mice. From these experiments, researchers identified the optimal LbL micro-needle structure, which appears to activate immune cells that are directly accessible on the skin. In living mice, these cells could in turn migrate into the lymphatic system and recruit other immune cells to attack the melanoma tumor. The researchers are now planning to test the patches on melanoma tumors in mice.
"We use low-cost chemistry and a simple manufacturing scheme to convert the vaccine," says Hammond. "Ultimately, we want to allow a device and put it on the market."
Micro-needle patch vaccine with RSV virus, immunostimulating compound, works against RSV
Synthetic charge-reversible polymer for rapid and complete implantation of layered microneedle drug films for improved transdermal vaccination, National Meeting and Exposure of the American Chemical Society (ACS), Autumn 2019.
The utility of layered (LbL) coated microneedle (MN) skin patches for transdermal drug delivery has been shown to be a promising approach that has advantages over subcutaneous injection because of its painless and simple self-administration. However, the long epidermal application time (15 to 90 minutes) required for drug implantation by existing LbL-MN strategies may lead to potential non-compliance with the medication. Here, we have developed an MN platform to shorten the time of application in MN therapies based on a synthetic, pH-induced, charge-reversible polymer of poly (2- (diisopropylamino) ethyl methacrylate-b-methacrylic acid) (PDM) One minute requires skin insertion time to implant LbL films in vivo. Following MN-mediated delivery of 0.5 μg of model antigen chicken egg ovalbumin (OVA) into the skin of mice, this system achieved a sustained release over 3 days and resulted in an increased immune response, significantly enhanced by humoral immunity compared to administration of OVA has been shown by conventional routes (subcutaneously and intramuscularly). In addition, in an ex vivo experiment on human skin, we achieved efficient immune activation by MN-administered LbL films as evidenced by the rapid uptake of vaccine adjuvants by the antigen-presenting cells. These features – rapid administration and the ability to induce a robust immune response – may potentially allow for a broad application of microneedle-based vaccination technologies.
Skin patches could release vaccines and cancer medicines painless in one minute (2019, 25th August)
26th August 2019 retrieved
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