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

Abstract

<jats:p> 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-PLEX<jats:sub>100</jats:sub> in abdominal surgical site. D-PLEX<jats:sub>100</jats:sub> 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-PLEX<jats:sub>100</jats:sub> 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-PLEX<jats:sub>100</jats:sub> mass was absorbed during the first 3 months, and by 6 months, D-PLEX<jats:sub>100</jats:sub> 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-PLEX<jats:sub>100</jats:sub> and its favorable degradability profile. A clinical study is being performed to assess the safety and the efficacy of D-PLEX<jats:sub>100</jats:sub> to prevent human abdominal SSIs. </jats:p>

Safety and efficacy of sFilm-FS, a novel biodegradable fibrin sealant, in Göttingen minipigs

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“…At the end of the absorption cycle, certain absorbable implants may leave trace amounts of process residue, such as mineralized debris, that become sequestered within giant cells or within a fibrous capsule or trapped within bone trabeculae, and assessed as innocuous 24 .…”

“…Biodegradable materials must be appropriately evaluated in preclinical studies; therefore, understanding the expected clinical and pathological outcomes from such studies is crucial. Although information on the expected pathological findings with the use of biodegradable materials in appropriate animal models is expanding 23 , 24 , 25 , 26 , 27 , 28 , information on biodegradable materials for hemostasis is still limited.…”

Preclinical In-Vivo Safety of a Novel Thyrotropin-Releasing Hormone-Loaded Biodegradable Nanoparticles After Intranasal Administration in Rats and Primates

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Intramedullary nail: the past, present and the future – a review exploring where the future may lead us

“…The safety and efficacy of PLEX have been trialed with the controlled release of doxycycline (doxycycline/polymerlipid encapsulation matrix [D-PLEX]) most recently in an abdominal surgery incision model of miniature swine. 37 The D-PLEX matrix did not show any evidence of systemic toxicities and was essentially absorbed at 6 months, demonstrating its safety and favorable degradability profile 37 However, further research is warranted to evaluate the safety and degradability profile in humans.…”