It’s been just over a year since the FDA issued a “Dear Veterinarian” letter that caught a lot of attention among livestock producers. The letter reminded veterinarians that aspirin and sodium salicylate are not approved for use in dairy cattle or any livestock.
“From an animal welfare standpoint, we know pigs go through pain. They have fevers and inflammation when they are sick. We can make them feel better with NSAIDs like we do in humans,” Brian Payne, senior director of commercial technical services R&D and innovation at Veterinary Pharmaceutical Solutions, said in a previous article. “When you’re feeling sick, you want to feel better. Pigs under our care should have that opportunity as well. When they have pain, inflammation or a fever, we can reduce that down so they start feeling better. A secondary benefit is that they produce better.”
To provide pain management and reduce repeated drug administration, Jeremy Powell, veterinarian and professor of animal science for the University of Arkansas System Division of Agriculture, joined a team of researchers to test an experimental pain-relieving drug delivery method for farm animals using microneedle patches.
Although the patches may not have delivered an effective dose, Powell says it took a pivotal step that offers new leads for innovation, according to a University of Arkansas release.
Two Birds With One Stone – Improving Pain and Welfare
The team wanted to find a way to provide analgesic therapy to help control pain in livestock species while improving animal welfare. The project, which began several years ago in cattle with meloxicam, has been supported by a USDA grant.
According to the release, initial studies led to unsatisfactory pain management for cattle. Because of this, the multi-state team of researchers received approval to switch the experiment to pigs using flunixin and dextran, other non-steroidal anti-inflammatory drugs that are more soluble than meloxicam.
The goal of the study was to alleviate some pain after castration and tail docking. Researchers set out to see if the patch could provide five to seven days of pain relief without daily injections or handling of the animal.
How Does the Microneedle Patch Work?
Researchers made the patches with polyvinyl alcohol, collagen and chitosan using a square mold. The patches are about 1"x1" and have 625 pyramid-shaped microneedles that are 800 microns tall — about the thickness of a stack of eight sheets of standard copy paper. The medicines were incorporated at a dose of 50 milligrams per patch, the study says.
Medicine slowly flows through the microneedles from the pain patches for slow-release drug delivery, the release explains. The patch is designed to eventually fall off and continue degrading into inert natural products that do not generate contaminants, says Jorge Almodovar, the study’s corresponding author and an associate professor in the department of chemical, biochemical and environmental engineering at the University of Maryland, Baltimore County, in the release.
“Designed to only penetrate the upper level of skin where there are few pain receptors, microneedles are known for being painless to mildly prickly, like pressing fine sandpaper when applied with light pressure, or a cat’s tongue brush,” the article says.
Although the drugs administered through the experimental patches did show up in the pigs’ system, the drug concentrations only reached about 2 micrograms per liter. Powell says they would need 3 milligrams per liter for the medicine to be effective, which is 1,500 times greater than what was achieved.
What’s Next for the Patch?
The project remains a proof of concept despite the limited performance, demonstrating that pig skin can absorb medication delivered through a dissolvable microneedle patch, the article says.
In the most recent published study, patches were applied to the ear and neck to assess anatomical site choice on systemic absorption. The team found patches work better on the neck than the ear, which Powell said may guide future testing.
The dextran-based patches on the neck achieved higher plasma concentrations than oral administration and ear-applied patches, “demonstrating enhanced uptake from vascularized regions,” the study explains. Meanwhile, the flunixin-based patches applied to the ear produced detectable plasma levels up to 72 hours after application, with a maximum concentration of about 1.9 micrograms per liter at 24 to 48 hours, “indicating sustained systemic exposure and reinforcing the potential for long-acting therapy.”
One of the other benefits of the patches was that no adverse responses were observed at application sites, the article says.
The findings emphasize the importance of choosing the right spot on the animal and using medications that the delivery method can handle are key to making microneedle drug delivery work better, the researchers note as they head back to the drawing board to improve the patch.
Editor’s Note: The study, “Systemic drug delivery in pigs using biodegradable microneedle patches,” was published in the journal RSC Pharmaceutics. The lead author, Katherine Miranda Muñoz, Ph.D., is a former graduate student at the University of Arkansas College of Engineering. Muñoz is now a postdoctoral associate at the University of Miami. Co-authors of the paper included Powell, Tsungcheng Tsai and Jacy L. Riddle in the department of animal science with the University of Arkansas System Division of Agriculture and Almodovar, Ke He and Lee Blaney at UMBC. Almodovar was previously an associate professor and Ray C. Adam Chair in Chemical Engineering at the University of Arkansas.
