Recipient Organization
UNIVERSITY OF ARKANSAS
(N/A)
FAYETTEVILLE,AR 72703
Performing Department
(N/A)
Non Technical Summary
Microneedle patches for transdermal drug delivery have shown promise in human healthcare but have been underutilized in veterinary medicine. Current approaches for administering medication to livestock suffer from harsh application approaches. We propose that a patch-type drug delivery method could simplify the industry's need for longer term drug administration. Our research team will plan to developed a biodegradable microneedle patch containing meloxicam to provide pain management during routine procedures. The goal of this project is to develop and evaluate the use of our engineered microneedle patch in cattle. This goal will be accomplished by evaluating our objectives regarding the efficacy of the engineered patch to manage pain of cattle following a castration procedure, and to assess the long term effect of the patch on cattle growth and behavior. We expect that the microneedle patch will deliver accurate doses of meloxicam for extended pain management. Successful completion of this project will result in novel technology to manage pain in cattle that is easier to implement than current strategies.
Animal Health Component
45%
Research Effort Categories
Basic
10%
Applied
45%
Developmental
45%
Goals / Objectives
Delivery of pain medication to animals is most often administered via injections or via oral tablets or suspension. These methods of drug administration often require repeated dosing which is not ideal for livestock owners and veterinarians. This project will study a better approach for long-term drug therapy for cattle. Our goal is to develop a transdermal microneedle patch made from the biodegradable substance chitosan, and evaluate its ability to administer meloxicam, a nonsteriodal anti-inflammatory drug, for pain control in cattle. This technology will deliver a convenient method to minimize or eliminate some of the negative impacts of post-surgical pain caused by procedures such as castration on cattle wellbeing, health and gain performance.Objective 1. To evaluate the efficacy of a novel transdermal microneedle chitosan patch to deliver consistent plasma concentrations of meloxicam to cattle.Objective 2. To evaluate the efficacy of a chitosan microneedle patch containing meloxicam for post-surgical physiologic and inflammatory response in castrated male calves.Objective 3. To evaluate the longterm effects of a meloxicam-chitosan microneedle patch on post-surgical behavior, growth performance and carcass quality when used to control post-surgical pain in male calves castrated at weaning.
Project Methods
This study will evaluate the chitosan needle patch for consistent delivery of meloxicam plasma concentrations as well as evaluate long term pain control and it effects on post-surgical physiologic response, behavioral response, growth performance and carcass quality in castrated male beef calves.Objective 1: In order to evaluate in vivo meloxicam plasma concentrations administered from a chitosan microneedle patch in male calves (n = 6), calves will be allocated randomly to treatments to provide 2 calves per each experimental treatment and 2 calves will serve as a negative control. Experimental treatments will consist of placing a single chitosan microneedle patch containing one of two different dosages of meloxicam on the inside of the calf's left ear. Blood samples will be collected via jugular venipuncture at 0, 20, 40 and 60 minutes; then 2, 4, 7, 10, 24, 30, 48, 72, 96, 120, 144, and 168 hours to evaluate meloxicam levels in blood plasma. The blood plasma samples will be sent to Kansas State University for HPLC and MS analysis to evaluate the two dosages of meloxicam levels in the blood plasma over time.Objective 2: Twenty-four calves will be assigned to 1 of 2 treatments (n = 12 calves/treatment) with the twelve bull calves randomly assigned to receive either a placebo (CON) or meloxicam-chitosan needle patch (MEL) prior to castration. On day one, cattle will be restrained in a squeeze chute for administration of the meloxicam-chitosan needle patches, and at the same time, an indwelling catheter will be placed into the jugular vein of all study animals to facilitate intensive, serial blood collection. Blood samples will be repeatedly collected from all calves at 0, 20, 40 and 60 minutes; then 2, 4, 7, 10, 24, 30, 48, 72, 96, 120, 144, and 168 hours to evaluate substance P, complete blood count, cortisol, prostaglandin E2, haptoglobin, cortisol and meloxicam plasma concentrations.Objective 3: Thirty-six male crossbred Angus calves will be obtained from a local farm and transported to the research unit. Calves will consist of bulls (n = 24) and steers (n = 12). Bull calves being randomly assigned to one of two treatments and the twelve steers serving as a negative control group. Twelve bulls will be randomly assigned to two treatments with twelve receiving a placebo chitosan patch and twelve receiving a meloxicam-chitosan needle patch 1 day prior to surgical castration. The twelve steer calves will serve as negative control (CON). Castration will be performed surgically on the bull calves. Calf behavioral activity will be monitored for the 28-day post-castration period on all calves using a 3-axis accelerometer attached to the right metatarsus using a plastic strap. Accelerometers will be attached to each calf from day 7 through day 28 to observe behavior. The accelerometers will log data every 15 minutes and the variables will include: time spent standing, time spent lying, number of steps taken, number of lying bouts, and a motion index determined from a proprietary algorithm. A baseline value for each behavior variable will be determined for each treatment by determining the behavior variable means recorded from days −7 to −1. During processing and castration on days -7, 0, 7, 14 and 28, animal temperament will be evaluated on each animal while restrained in the hydraulic squeeze chute using a 4-point scale. The evaluator will be masked to drug treatment. Calves will be monitored throughout the entire study for general health and well-being. Individual body weights will be recorded throughout the study on days -7, 0, 7, 14, 28, 56, 84, 112, 140, 168 182 (feedlot entry), interim feedlot weight, and harvest weight. Stalls will be randomly assigned to calves upon arrival, and calves be given a 2-week acclimation period before study commencement. After day 28 of the study, calves will be commingled and moved to a series of twelve 2.4 ha pens and grazed as a single group being rotated through the pastures to supply adequate forage needs. The pens will contain mixed-grass forage and calves will be maintained there for an additional 152-day period to complete the grazing phase of the study. During grazing, the feed management approach will designed to provide cattle with ad libitum hay if forage is limiting and a supplemental commodity ration intended to achieve approximately 0.68 kg of gain/d which will be fed daily. Around day 200, calves will be shipped to a feedlot and fed a total mixed ration until reaching harvest weight. Calves will be assigned to a single feedlot pen and fed a common feedlot ration throughout the finishing period. When steers are determined by feedlot personnel to reach a suitable degree of finish, they will be transported to a commercial processing plant for harvest. Backfat thickness, rib eye area, HCW, marbling score, quality grade, and yield grade data will recorded at harvest of the study calves by a trained technician.