International Journal of Nanomedicine (Feb 2020)
The Safety and Exploration of the Pharmacokinetics of Intrapleural Liposomal Curcumin
Abstract
Ashleigh Hocking,1 Sara Tommasi,2 Peter Sordillo,3 Sonja Klebe1,4 1Department of Anatomical Pathology, Flinders University, Adelaide, SA, Australia; 2Department of Clinical Pharmacology, Flinders University, Adelaide, SA, Australia; 3SignPath Pharma Inc, New York, NY, USA; 4Department of Surgical Pathology, SA Health, Flinders Medical Centre, Bedford Park, SA, AustraliaCorrespondence: Ashleigh HockingDepartment of Anatomical Pathology, Flinders University, Flinders Medical Centre, Flinders Drive, Bedford Park, SA 5041, AustraliaEmail [email protected]: Malignant pleural effusion (MPE) is the accumulation of fluid in the pleural cavity as a result of malignancies affecting the lung, pleura and mediastinal lymph nodes. Curcumin, a compound found in turmeric, has anti-cancer properties that could not only treat MPE accumulation but also reduce cancer burden. To our knowledge, direct administration of curcumin into the pleural cavity has never been reported, neither in animals nor in humans.Purpose: To explore the compartmental distribution, targeted pharmacokinetics and the safety profile of liposomal curcumin following intrapleural and intravenous administration.Methods: Liposomal curcumin (16 mg/kg) was administered into Fischer 344 rats by either intrapleural injection or intravenous infusion. The concentration of curcumin in plasma and tissues (lung, liver and diaphragm) were measured using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Blood and tissues were examined for pathological changes.Results: No pleural or lung pathologies were observed following intrapleural liposomal curcumin administration. Total curcumin concentration peaked 1.5 hrs after the administration of intrapleural liposomal curcumin and red blood cell morphology appeared normal. A red blood cells abnormality (echinocytosis) was observed immediately and at 1.5 hrs after intravenous infusion of liposomal curcumin.Conclusion: These results indicate that liposomal curcumin is safe when administered directly into the pleural cavity and may represent a viable alternative to intravenous infusion in patients with pleural-based tumors.Keywords: malignant pleural effusion, liposomal, curcumin, intrapleural, local administration
