D-PLEX₁₀₀ in an Abdominal Surgery Incision Model in Miniature Swine: Safety Study

Surgical site infections (SSIs) are a common surgical-related complication. To avoid these complications, a new biodegradable polymer-lipid encapsulation matrix that provides controlled release of doxycycline (doxycycline/polymer-lipid encapsulation matrix [D-PLEX]) has been developed. The aim of this comprehensive study was to evaluate the potential safety of D-PLEX₁₀₀ in abdominal surgical site. D-PLEX₁₀₀ was administered into incisions of abdominal surgical site in Yucatan miniature swine, which were followed for up to 6 months and compared to sham-control swine. The D-PLEX₁₀₀ mass did not migrate from the incisional site, and there was no evidence for systemic toxicity or other safety concerns. Surgical incision sites, including the peritoneal surface, were fully healed at 6 months in all animals. Most of the D-PLEX₁₀₀ mass was absorbed during the first 3 months, and by 6 months, D-PLEX₁₀₀ was fully absorbed. Toxicokinetic evaluation revealed that doxycycline concentrations were evident at 30 minutes and persisted to 8 days (71 mg/kg) or at least 15 days (284 mg/kg) and were no longer present in plasma by day 29. This study supports the safety of D-PLEX₁₀₀ and its favorable degradability profile. A clinical study is being performed to assess the safety and the efficacy of D-PLEX₁₀₀ to prevent human abdominal SSIs.