Design, characterization, and modeling of a chitosan microneedle patch for transdermal delivery of meloxicam as a pain management strategy for use in cattle

David A Castilla-Casadiego; Hayden Carlton; David Gonzalez-Nino; Katherine A Miranda-Muñoz; Raheleh Daneshpour; David Huitink; Gary Prinz; Jeremy Powell; Lauren Greenlee; Jorge Almodovar

doi:10.1016/j.msec.2020.111544

Design, characterization, and modeling of a chitosan microneedle patch for transdermal delivery of meloxicam as a pain management strategy for use in cattle

Mater Sci Eng C Mater Biol Appl. 2021 Jan:118:111544. doi: 10.1016/j.msec.2020.111544. Epub 2020 Sep 23.

Affiliations

¹ Ralph E. Martin Department of Chemical Engineering, University of Arkansas, 3202 Bell Engineering Center, Fayetteville, AR 72701, USA.
² Department of Mechanical Engineering, University of Arkansas, 204 Mechanical Engineering Building, Fayetteville, AR 72701, USA.
³ Department of Civil Engineering, University of Arkansas, 4190 Bell Engineering Center, Fayetteville, AR 72701, USA.
⁴ Department of Biomedical Engineering, College of Engineering, University of Arkansas, Fayetteville, AR 72701, USA.
⁵ Department of Animal Sciences, University of Arkansas, B110 Agriculture, Food and Life Sciences Building, Fayetteville, AR 72701, USA.
⁶ Ralph E. Martin Department of Chemical Engineering, University of Arkansas, 3202 Bell Engineering Center, Fayetteville, AR 72701, USA. Electronic address: jlalmodo@uark.edu.

PMID: 33255096
DOI: 10.1016/j.msec.2020.111544

Abstract

This work describes the formulation and evaluation of a chitosan microneedle patch for the transdermal delivery of meloxicam to manage pain in cattle. Microneedle patches composed of chitosan and chitosan/meloxicam were evaluated regarding their chemical composition, uniformity of physical characteristics, capacity to penetrate the skin, and response to thermal and thermo-mechanical changes. Microneedle patches were prepared by varying the percentage of acetic acid used during solution preparation, including 90% (v/v), 50% (v/v), and 10% (v/v). In addition, drug release was assessed by modeling different percentages of penetration into the skin and the number of microneedles on the microneedle patch. Scanning electron microscopy confirmed the presence of microneedles uniformly organized on the patch surface for each percentage of acetic acid used. Fourier transform infrared spectroscopy revealed that 10% (v/v) of acetic acid in the solution was a suitable condition to preserve the characteristic bands of chitosan (amide I and amide II) and meloxicam (amine NH stretch and CO stretch) as compared to 90% (v/v) and 50% (v/v) of acetic acid used during the solution preparation. The resultant microneedle patches were successful in penetrating the skin in a cow's cadaver ear. Results demonstrated that the average depth penetration measured after complete dehydration of the penetrated skin was approximately 78 ± 1 μm. Chitosan and chitosan/meloxicam microneedle patches with higher acetic acid percentages reflected greater resistance to compressive force as temperature increased. Time-dependent simulation of the transport of diluted species by COMSOL revealed that the transdermal drug delivery increases in function to the increment of the number of microneedles on the surface patch and percentage of penetration per microneedle. One patch released a drug concentration of 3.57 × 10^-5 mol/m³ in the skin per week, which represents the 26.2% of what is needed for pain management in cattle, established as 1.43 × 10^-4 mol/m³. These results demonstrate that chitosan/meloxicam microneedles patches may be suitable to manage pain in cattle after routine procedures.

Keywords: Animal welfare; Biodegradable microneedle; Chitosan; Meloxicam; Transdermal drug delivery.

MeSH terms

Administration, Cutaneous
Animals
Cattle
Chitosan*
Drug Delivery Systems
Female
Meloxicam
Needles
Pain Management
Skin
Transdermal Patch

Substances

Chitosan
Meloxicam