Ivermectin is a widely used antiparasitic drug with known efficacy against several single-strain RNA viruses. Recent data shows significant reduction of SARS-CoV-2 replication in vitro by ivermectin concentrations not achievable with safe doses orally. Inhaled therapy has been used with success for other antiparasitics. An ethanol-based ivermectin formulation was administered once to 14 rats using a nebulizer capable of delivering particles with alveolar deposition. Rats were randomly assigned into three target dosing groups, lower dose (80-90 mg/kg), higher dose (110-140 mg/kg) or ethanol vehicle only. A toxicology profile including behavioral and weight monitoring, full blood count, biochemistry, necropsy and histological examination of the lungs was conducted. The pharmacokinetic profile of ivermectin in plasma and lungs was determined in all animals. There were no relevant changes in behavior or body weight. There was a delayed elevation in muscle enzymes compatible with rhabdomyolysis, that was also seen in the control group and has been attributed to the ethanol dose which was up to 11 g/kg in some animals. There were no histological anomalies in the lungs of any rat. Male animals received a higher ivermectin dose adjusted by adipose weight and reached higher plasma concentrations than females in the same dosing group (mean Cmax 86.2 ng/ml vs. 26.2 ng/ml in the lower dose group and 152 ng/ml vs. 51.8 ng/ml in the higher dose group). All subjects had detectable ivermectin concentrations in the lungs at seven days post intervention, up to 524.3 ng/g for high-dose male and 27.3 ng/g for low-dose females. nebulized ivermectin can reach pharmacodynamic concentrations in the lung tissue of rats, additional experiments are required to assess the safety of this formulation in larger animals.

Background: Capsular contracture is the most common complication associated with silicone prostheses. It may take the form of anything from slight hardening to obvious deformity. The role of transforming growth factor beta (TGF-beta) in the scar physiopathology of any fibrotic process has been demonstrated. The effects of inhibition of TGF-beta have also been demonstrated in experimental models of fibrosis, which opens the way for new therapeutic alternatives in the treatment of capsular contracture. The aim of this study was to evaluate periprosthetic fibrosis with a newly synthesized TGF-beta peptide inhibitor (p144). Methods: Three experimental groups were formed: Group I, subcutaneous and submuscular textured silicone prostheses were left untreated; Group 2, the prostheses were left after being immersed in the vehicle; Group 3, the same protocol was followed as in Group 2, but the solution contained the vehicle with the inhibitor peptide of TGF-beta, p144 (15 mg/prosthesis). The animals were sacrificed 24 weeks after implantation, and the capsules were assessed both macroscopically and histologically. Results: The results obtained showed that the inhibition of capsular thickness and soluble collagen content in pericapsular fibrosis did not significantly decrease in the group of animals treated with the TGF-beta inhibitor peptide in comparison with control cases. Conclusions: We detected no statistically significant reduction in fibrosis in the periprosthetic capsule after treating the implants with the inhibitor peptide p144, but we feel that the influence of trauma around the prosthesis is critical in impeding the antifibrotic activity of the inhibitor peptide.