Description of a novel approach for intraperitoneal drug delivery and the related device
- 655 Downloads
Two significant limitations of intraperitoneal drug therapy are limited drug distribution and poor penetration into peritoneal nodules. A possible solution is the application of the so-called “therapeutic pneumoperitoneum,” taking advantage of the gaseous nature and the pressure of capnoperitoneum during laparoscopy. Our objective was to develop a device able to apply such therapeutic pneumoperitoneum.
The technology presented here is a spraying device and can be introduced through a trocar. It is driven by mechanical pressure and consists of an injector, a line, and a nozzle. An in vivo experimental study was performed in five pigs. A transvaginal cholecystectomy was performed. At the end of the procedure, a standard dose of methylene blue was sprayed/infused into the abdominal cavity for 30 min (4 test animals w/therapeutic pneumoperitoneum (12 mmHg CO2) and 1 control animal w/conventional lavage (2 l intra-abdominal volume with extracorporeal circulation)). At the end of the procedure, all animals were autopsied and the peritoneum was analyzed. Outcome criteria were: (1) drug distribution (as assessed by the stained peritoneal surface at autopsy), and (2) diffusion into the peritoneum (presence or not of macroscopic staining of the outer aspect of the peritoneum immediately after surgery).
Stained peritoneal surface was larger after aerosol application compared with peritoneal lavage, and staining more intense. Hidden peritoneal surfaces and the anterior abdominal wall were stained only in the aerosol group. In contrast to peritoneal lavage, the outer aspect of peritoneal membrane was immediately stained after pressurized spraying.
This device and the related approach significantly improve both distribution and penetration of a test substance into the peritoneal cavity in a large animal model. This might be a significant progress in treating intraperitoneal disease, in particular peritoneal carcinomatosis.
KeywordsLaparoscopic surgery Peritoneum-therapy Nebulizer Cancer Pneumoperitoneum Drug delivery Pharmacokinetics
This study was funded by Reger Medizintechnik GmbH, Rottweil, Germany. Alexander Hetzel is employed by and has an equity interest in Reger Medizintechnik. Wiebke Solaß, Giorgi Nadiradze, Emil Sagynaliev, and Marc A. Reymond have no conflicts of interest or financial ties to disclose.
- 4.Elias D, Lefevre JH, Chevalier J, Brouquet A, Marchal F, Classe JM, Ferron G, Guilloit JM, Meeus P, Goéré D, Bonastre J (2009) Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin. J Clin Oncol 27:681–685PubMedCrossRefGoogle Scholar
- 5.Alberts DS, Liu PY, Hannigan EV, O’Toole R, Williams SD, Young JA, Franklin EW, Clarke-Pearson DL, Malviya VK, DuBeshter B (1996) Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer. N Engl J Med 335:1950–1955PubMedCrossRefGoogle Scholar
- 12.Druckrey-Fiskaaen KT, Janssen MW, Omidi L, Polze N, Kaisers U, Nur I, Goldberg E, Bokel G, Hauss J, Schön MR (2007) Laparoscopic spray application of fibrin sealant effects on hemodynamics and spray efficiency at various application pressures and distances. Surg Endosc 21:1750–1759PubMedCrossRefGoogle Scholar
- 16.Steller MA, Egorin MJ, Trimble EL, Bartlett DL, Zuhowski EG, Alexander HR, Dedrick RL (1999) A pilot phase I trial of continuous hyperthermic peritoneal perfusion with high-dose carboplatin as primary treatment of patients with small-volume residual ovarian cancer. Cancer Chemother Pharmacol 43:106–114PubMedCrossRefGoogle Scholar