Oxfendazole

Strongyloides stercoralis is a worldwide occurring nematode infecting canids and primates (including humans), responsible for a largely underestimated zoonotic disease. We here present 18 cases including overall 20 dogs affected by S. stercoralis, diagnosed in Switzerland between 2010 and 2020. The Baermann examination was positive for S. stercoralis larvae in 10, suspicious in 4, negative in one and not performed in 2 dogs. In 3 dogs the infection was identified only at necropsy by histology or by direct faecal or mucosal smears from intestinal tissue. Confirmation of suspected, necropsied and Baermann-negative dogs relied on genetic analyses. Twelve dogs had a history of import from Eastern Europe (n=4), the Mediterranean basin (n=5) or Germany (n=3). They were 7 weeks to 9,5 months old, and also the dogs supposedly born in Switzerland were younger than one year (except two, aged 15 months and 14 years). Thirteen dogs were males and 6 females (1 unknown). The most represented breeds were Chihuahuas (n=5), French Bulldogs (n=4) and Pomeranians (n=3). The most frequent clinical sign and reason for presentation was diarrhoea, occurring in 11/20 animals. Further gastrointestinal symptoms were vomiting, anorexia/hyporexia, adipsia, dehydration, tense abdomen and tenesmus. Respiratory symptoms were the second most frequent, with coughing in 7/20 animals, followed by tachypnoea/dyspnoea in 5 and (reverse) sneezing in 3 dogs. Treatment with 50 mg/kg BW fenbendazole p.o. over 5 days was successful in 4 cases in which a follow-up examination was performed 3-6 weeks later; prolonged treatment over 21 days was also effective. Ivermectin off-label protocols described in the literature, e.g. 0,8 mg/kg BW s.c. or 0,5 mg/kg BW i.m. repeated after 2 weeks, were successful based on control examinations performed 3-10 weeks later. Strongyloides stercoralis infections are clinically relevant, potentially zoonotic and need to be included in differential diagnoses in case of canine gastrointestinal and respiratory disorders, especially in young and imported dogs.

Fenbendazole is a broad-spectrum anthelmintic used in veterinary medicine. It is a lipophilic benzimidazole derivative with low water solubility (<0.1 g/L) recently studied for repositioning in cancer treatment. These potential new uses highlight the need for new dosage forms. Thus, chitosan-crosslinked microparticles were prepared by spray drying, applying a Design of Experiments approach to optimize the composition of the microparticles, evaluating the type and mass of chitosan and crosslinking agent, alongside crosslinking reaction time. The recovered optimized microparticles were characterized by infrared spectroscopy, and changes in the drug crystalline phase were studied by differential scanning calorimetry and X-ray powder diffraction, further confirmed by wide-angle X-ray scattering. After encapsulation of fenbendazole in the chitosan-crosslinked matrix, the resulting microparticles had a particle size of 2.43 μm with a polydispersion index of 0.754 and a Zeta potential value of + 49.85 mV. In vitro dissolution showed that the optimized microparticles had an improved dissolution profile compared to the non-encapsulated drug. The analysis of the encapsulated drug in the solid state showed a remarkable reduction of its crystalline properties. In conclusion, these results demonstrate that fenbendazole encapsulation into an optimized chitosan-crosslinked matrix leads to better biopharmaceutical performance.