University of Maryland Baltimore County, United States
Introduction: This research addresses the critical need for effective pain management in farm animals during routine procedures like castration, tail docking, and dehorning. These procedures, essential for husbandry, often cause considerable pain due to the lack of anesthesia, posing challenges to animal welfare and productivity. The study focuses on developing biodegradable microneedle patches for transdermal delivery of meloxicam, an effective analgesic. Integrating material science, pharmacology, and veterinary medicine, we aim to provide a comprehensive solution to enhance animal welfare and productivity in agriculture. Aligned with global concerns for animal welfare in food production, our project utilizes polyvinyl alcohol (PVA), type I collagen (COL), and chitosan (CHI) to enhance drug release kinetics and mechanical properties. Through in vitro and in vivo studies, including dissolution, imaging, and transdermal delivery assessments, we aim to optimize meloxicam diffusion. Our research contributes to advancing pain management practices in agriculture by evaluating the efficacy of the PVA-COL-CHI-MEL microneedle patch system. The implications of this study extend to veterinary professionals, producers, and regulatory bodies involved in farm animal welfare. By offering an effective pain relief solution, our research aims to enhance animal welfare standards, productivity, and consumer confidence in food production systems.
Materials and
Methods: In vitro drug diffusion studies were conducted using a ballistic gel model to simulate microneedle performance without biological variability (Fig. 1C). SEM analysis depicted the sequential dissolution of PVA-COL-CHI-MEL microneedle patches at various time points over 24 hours. In vitro imaging in pig's ear cadaver skin demonstrated effective microneedle penetration and degradation over time. In vivo studies involved attaching microneedle patches to porcine ears and assessing their dissolution and drug delivery capabilities (Fig.1D). Plasma meloxicam concentrations were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry.
Figure 1. Comprehensive study and application of microneedle patch technology for transdermal drug delivery in veterinary medicine. A) Macroscopy picture of the microneedle patch and schematic illustrations of transdermal delivery of meloxicam using PVA-COL-CHI-MEL microneedle patches. B) Veterinary applications of microneedle patches. C) Microneedle insertion set up on ballistic gel (top layer: adhesive waterproof tape) and schematic microneedle dissolution. D) In-Vivo Setup: Preparing the pig's inner and outer ear surface for microneedle patch application. E) SEM micrographs demonstrating sequential microneedle patch dissolution at different time points. F) In-vitro imaging of microneedle insertion in pig's ear cadaver skin. G) Schematic of the in-vitro setup for monitoring drug delivery from the microneedles, using a Shimadzu 20A prominence High-Performance Liquid Chromatography (HPLC) system for quantification over time. In-vitro cumulative release profile of meloxicam from the microneedle patch, plotted over 18 hours. H) Plasma meloxicam concentrations using a microneedle patch for drug delivery.
Results, Conclusions, and Discussions: In vitro studies revealed a consistent degradation pattern of microneedles in ballistic gel, with SEM images depicting a gradual reduction in height over 24 hours (Fig. 1E). In vitro imaging demonstrated successful penetration and dissolution of microneedles in pig's ear cadaver skin, corroborated by histological evaluations (Fig. 1F). In vitro drug release analysis showcased sustained release kinetics of meloxicam, achieving nearly 100% release within 18 hours (Fig 1G). In vivo dissolution studies indicated over 70% microneedle dissolution after 3 days (Fig. 1G). Plasma meloxicam concentrations demonstrated successful drug delivery through microneedle patches, although with some variability attributed to placement and animal behavior (Fig. 1H).
Conclusions: The study underscores the potential of biodegradable microneedle patches for veterinary drug delivery, evidenced by their controlled dissolution, sustained drug release, and transdermal delivery capabilities. Despite observed variations, the patches exhibited significant drug delivery potential, highlighting the need for further optimization and control of variables in future studies. These findings lay the groundwork for enhancing veterinary anesthesia and therapeutic applications through innovative microneedle technology.
