The transdermal delivery of non-steroidal anti-inflammatory drugs (NSAIDs) has the potential to overcome some of the major disadvantages relating to oral NSAID usage, such as gastrointestinal adverse events and compliance. However, the poor solubility of many of the newer NSAIDs creates challenges in incorporating the drugs into formulations suitable for application to skin and may limit transdermal permeation, particularly if the goal is therapeutic systemic drug concentrations. This review is an overview of the various strategies used to increase the solubility of poorly soluble NSAIDs and enhance their permeation through skin, such as the modification of the vehicle, the modification of or bypassing the barrier function of the skin, and using advanced nano-sized formulations. Furthermore, the simple yet highly versatile microemulsion system has been found to be a cost-effective and highly successful technology to deliver poorly water-soluble NSAIDs.

Mass spectrometry-based plasma proteomics offers a major advance for biomarker discovery in the veterinary field, which has traditionally been limited to quantification of a small number of proteins using biochemical assays. The development of foundational data and tools related to sequential window acquisition of all theoretical mass spectra (SWATH)-mass spectrometry has allowed for quantitative profiling of a significant number of plasma proteins in humans and several animal species. Enabling SWATH in dogs enhances human biomedical research as a model species, and significantly improves diagnostic and disease monitoring capability. In this study, a comprehensive peptide spectral library specific to canine plasma proteome was developed and evaluated using SWATH for protein quantification in non-depleted dog plasma. Specifically, plasma samples were subjected to various orthogonal fractionation and digestion techniques, and peptide fragmentation data corresponding to over 420 proteins was collected. Subsequently, a SWATH-based assay was introduced that leveraged the developed resource and that enabled reproducible quantification of 400 proteins in non-depleted plasma samples corresponding to various disease conditions. The ability to profile the abundance of such a significant number of plasma proteins using a single method in dogs has the potential to accelerate biomarker discovery studies in this species.

Dogs undergo various surgical procedures such as castration, ovariohysterectomy, and other orthopedic procedures, which are known to cause inflammation and pain. Non-steroidal anti-inflammatory drugs (NSAIDs) are very effective analgesics for alleviating postoperative pain in veterinary medicine. Ketoprofen is currently approved in Australia and the United States for treating different painful conditions in dogs. This study evaluated the pharmacokinetic parameters of ketoprofen after intravenous (IV) and transdermal (TD) administration in healthy dogs. A novel transdermal ketoprofen (TDK) formulation containing 20% ketoprofen, dissolved in a combination of 45:45% isopropanol and Transcutol, along with 10% eucalyptus oil, was developed and evaluated for in vitro dermal permeation using Franz diffusion cells. A crossover study was then conducted to determine the pharmacokinetic parameters of the formulation in six dogs following IV ketoprofen (1 mg/kg) and TDK (10 mg/kg) administration. A liquid chromatography–mass spectrometry (LC-M/MS) method was used to measure plasma concentrations of ketoprofen over time, and a non-compartmental analysis determined the pharmacokinetic parameters. The mean terminal elimination half-life (T_½ h), AUC_0-t (µg·h/mL), and mean residence time (MRT, h) between IV and TDK groups were 4.69 ± 1.33 and 25.77 ± 22.15 h, 15.75 ± 7.72 and 8.13 ± 4.28 µg·h/mL, and 4.86 ± 1.81 and 41.63 ± 32.33 h, respectively. The calculated bioavailability (F%) was ~7%, with a lag time of 30 min to achieve effective plasma concentrations after the application of TDK.

Establishing plasma biomarkers in the veterinary field has always been a challenge, due to a lack of significant understanding of pathophysiological attributes of disease. Advances in mass spectrometry-based proteomic techniques have improved plasma biomarker discovery in veterinary medicine. Feline hypertrophic cardiomyopathy is the most common cardiac disease in cats and has a complex and not fully elucidated pathophysiology. This study aimed to use SWATH-MS proteomics to identify novel plasma biomarkers for fHCM and to further elucidate disease pathogenesis. Plasma was collected from 20 cats, consisting of healthy controls (n = 10) and a HCM group (n = 10). Cats with fHCM, were diagnosed by echocardiography and disease statuses were determined by a veterinary cardiologist. Undepleted cat plasma samples were digested using FASP and quantitative analysis was performed using DIA-NN. A total of 40 plasma proteins were found to be dysregulated, primarily associated with innate and humoral responses, including complement C7 and C9 and properdin proteins. Other dysregulated proteins were involved in blood coagulation (fibrinogen, fibulin-1), lipid metabolism (apolipoproteins), and inflammation pathways (transthyretin and plasminogen). These findings provide possible biomarkers for fHCM, with the potential to detect disease before clinical signs become evident, which is a significant outcome for fHCM. These proteomic changes suggest critical pathways for earlier intervention and could potentially lead to more effective treatment outcomes. Furthermore, having significant similarity to human disease strengthens the case for using cats as a potential translational model for hHCM.

Objective: Explore potential associations between sublingual microcirculatory measures and plasma plasminogen activator inhibitor‐one concentrations in patients attending the kidney transplant assessment clinic and healthy controls. Methods: A single‐center cohort study was performed by retrospectively recruiting 44 kidney transplant assessment clinic attendees and 15 nested non‐renal failure controls who were selected from a larger pool ( N = 44). The nested controls were frequency matched to the kidney transplant assessment clinic cohort by sex, ethnicity and diabetes. Sidestream dark field videomicroscopy (MicroScan, Microvision Medical, Amsterdam) of the sublingual microcirculation allowed quantification of five microcirculatory parameters in all patients: total vessel density, microvascular flow index, portion of perfused vessels, heterogeneity index and perfused vessel density. Plasma plasminogen activator inhibitor‐one concentrations were determined using sandwich ELISA. Median (IQR) were reported for non‐normally distributed data. Mann–Whitney‐Wilcoxon tests were performed to compare the distribution of ranks between non‐normally distributed groups ( U ‐statistic) with p < 0.05 considered statistically significant. The Benjamini–Hochberg adjustment was applied to nominal p ‐values ( q ‐value) to account for inflation of the false discovery rate across multiple exploratory analyses, with q < 0.05 considered statistically significant. Results: Plasminogen activator inhibitor‐one levels were significantly higher in controls than those attending the transplant clinic (18.0 (11.5), 10.2 (6.8) ng/mL; U = 158, p = 0.006). Among kidney transplant patients, nominal associations revealed PAI‐1 was inversely correlated with hemodynamic parameters perfused vessel density ( p = 0.04, r = −0.32) and microvascular flow index ( p = 0.01, r = −0.38); neither survived the Benjamini–Hochberg adjustment ( q = 0.24 and q = 0.12, respectively). No other correlations between PAI‐1 and any of the sublingual microcirculatory measures survived the Benjamini–Hochberg adjustment in both cohorts. Conclusion: PAI‐1 is potentially associated with maladaptive hemodynamic changes in the sublingual microcirculation, implying its dysregulation may potentiate microvascular dysfunction. The results, however, must be interpreted with caution as no associations survived the Benjamini–Hochberg correction.