Release of doxorubicin from its liposomal coating via high intensity ultrasound
The present ex vivo study was performed to analyze the impact of high intensity ultrasound (HIUS) on penetration depth and particle stability of liposomal doxorubicin (LD) on the peritoneal surface. Fresh post mortem swine peritoneum was cut into proportional sections and subjected to a previously established ex vivo model of pressurized intraperitoneal aerosol chemotherapy (PIPAC). Samples were treated with 50 ml NaCl (0.9%) containing 3 mg LD via PIPAC or lavage. In both groups, half of the samples received additional HIUS treatment. Samples treated via PIPAC were covered with a 30-mm-thick abdominal muscle wall tissue, fatty tissue and skin, followed by transcutaneous HIUS. Samples administered with LD via lavage received close-range contact HIUS. Doxorubicin tissue penetration was measured using fluorescence microscopy on frozen sections. Liposomal integrity on peritoneal surfaces was measured via electron microscopy (EM). Mean penetration rates of doxorubicin were significantly higher with HIUS in combination with PIPAC or lavage compared with PIPAC alone (P<0.001) or lavage alone (P<0.00001). LD was not detected on the peritoneal surface via EM analysis in either group following HIUS. The present data suggested that HIUS may be a feasible application that can facilitate the release of doxorubicin from its liposomal envelope. HIUS was effective in both close-range, in contact with the samples, and through the abdominal wall. The present approach may be used in the future for both endoscopic and open lavage of the peritoneal cavity with LD in intraperitoneal chemotherapeutic applications such as hyperthermic intraperitoneal chemotherapy or PIPAC.