Biodegradable microneedle patch for delivery of meloxicam for managing pain in cattle.

Microneedle patches are a promising source for transdermal diffusion of macromolecules and are designed to painlessly penetrate the skin. In this study, a biodegradable chitosan microneedle patch to deliver meloxicam for managing pain in cattle was tested. The potential of reuse of the polymeric solution to fabricate the patches, optimization of fabrication, morphological analysis of the microneedle patch and analysis of preservation of the chemical composition after sterilization were evaluated. In-vitro analysis consisted of studying in-vitro penetration mechanical properties, compression testing analysis of microneedle patch, and in-vitro drug release analysis. In-vivo studies were performed to analyze the dissolution capability of the microneedle patch. Results regarding the physical characteristics, chemical composition, and mechanical properties confirmed that rheological properties of the chitosan solution, present significant differences over time, demonstrating that reusing the solution on the fourth day results in failure patches. Morphological characteristics and chemical composition studies revealed that the process of sterilization (ethylene oxide gas) needed for implanting the patches into the skin did not affect the properties of microneedle patches. In-vitro studies showed that approximately 33.02 ± 3.88% of the meloxicam was released over 7 days. A full penetration of the microneedles into the skin can be obtained by applying approximately 3.2 N. In-vivo studies demonstrated that microneedle patches were capable of swelling and dissolving, exhibiting a dissolution percentage of more than 50% of the original height of microneedle after 7 days. No abnormal tissue, swelling, or inflammation was observed in the implanted area. The results of this work show that chitosan biodegradable microneedle patches may be useful to deliver meloxicam to improve pain management of cattle with positive effects for commercial manufacturing.

Micromechanical Tension Testing of Additively Manufactured 17-4 PH Stainless Steel Specimens.

This study presents a methodology for the rapid fabrication and micro-tensile testing of additively manufactured (AM) 17-4PH stainless steels by combining photolithography, wet-etching, focused ion beam (FIB) milling, and modified nanoindentation. Detailed procedures for proper sample surface preparation, photo-resist placement, etchant preparation, and FIB sequencing are described herein to allow for high throughput (rapid) specimen fabrication from bulk AM 17-4PH stainless steel volumes. Additionally, procedures for the nano-indenter tip modification to allow tensile testing are presented and a representative micro specimen is fabricated and tested to failure in tension. Tensile-grip-to-specimen alignment and sample engagement were the main challenges of the micro-tensile testing; however, by reducing the indenter tip dimensions, alignment and engagement between the tensile grip and specimen were improved. Results from the representative micro-scale in situ SEM tensile test indicate a single slip plane specimen fracture (typical of a ductile single crystal failure), differing from macro-scale AM 17-4PH post-yield tensile behavior.

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

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.