title: High Penetration of Paclitaxel in Abdominal Wall of Rabbits after Hyperthermic Intraperitoneal Administration of Nab-Paclitaxel Compared to Standard Paclitaxel Formulation.
abstract: Paclitaxel (PTX) is currently used in combination with cisplatin for Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for the treatment of peritoneal carcinomatosis. Albumin-bound PTX is a promising new drug for HIPEC because of its easy solubility in aqueous perfusion medium and possibly because of the tendency of albumin to cross physiological barriers and accumulate in tumor tissue.
  
  
  
  We tested the feasibility of using nab-paclitaxel in rabbits treated by HIPEC for 60 min compared with the classical formulation at an equivalent PTX dose. Samples of perfusate and blood were collected at different time points and peritoneal tissues were collected at the end of perfusion. PTX concentrations were determined by HPLC. The depth of paclitaxel penetration through the peritoneal barrier was assessed by mass spectrometry imaging.
  
  
  
  PTX after nab-paclitaxel treatment penetrated up to 0.63 mm in the peritoneal wall, but after CRE-paclitaxel, it was not detectable in the peritoneum. Moreover, the peritoneal concentration after nab-paclitaxel was five times that after paclitaxel classical formulation. Despite the high levels reached in the peritoneum, systemic exposure of PTX was low.
  
  
  
  Our results show that nab-paclitaxel penetrates into the abdominal wall better than CRE-paclitaxel, in terms of effective penetration and peritoneal tissue concentration.
authors.affiliation: General, Emergency and Trauma Surgery Department Papa Giovanni XXIII hospital, Bergamo, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Coccolini
authors.affiliation: Dipartimento di Scienze Veterinarie per la Salute, la Produzione Animale e la Sicurezza Alimentare, Università degli Studi di Milano, Milan, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Acocella
authors.affiliation: Oncology Department, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. lavinia.morosi@marionegri.it.
authors.forename: Lavinia
authors.identifier: 0000-0003-1301-720X
authors.initials: L
authors.lastname: Morosi
authors.affiliation: Dipartimento di Scienze Veterinarie per la Salute, la Produzione Animale e la Sicurezza Alimentare, Università degli Studi di Milano, Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Brizzola
authors.affiliation: Dipartimento di Scienze Veterinarie per la Salute, la Produzione Animale e la Sicurezza Alimentare, Università degli Studi di Milano, Milan, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Ghiringhelli
authors.affiliation: General, Emergency and Trauma Surgery Department Papa Giovanni XXIII hospital, Bergamo, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Ceresoli
authors.affiliation: Mass Spectrometry Laboratory, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Davoli
authors.affiliation: General, Emergency and Trauma Surgery Department Papa Giovanni XXIII hospital, Bergamo, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Ansaloni
authors.affiliation: Oncology Department, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: D'Incalci
authors.affiliation: Oncology Department, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Zucchetti
mesh_terms: D034861:Abdominal Wall / Q000502:physiology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D004339:Drug Compounding; D015195:Drug Design; D005260:Female; D006979:Hyperthermia, Induced / Q000379:methods*; D007274:Injections, Intraperitoneal; D053758:Nanoparticles / Q000737:chemistry; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D010316:Particle Size; D065629:Peritoneal Absorption; D010534:Peritoneal Neoplasms / Q000188:drug therapy; D010539:Permeability; D011817:Rabbits; D013499:Surface Properties; D014018:Tissue Distribution
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel
keywords: intraperitoneal chemoterapy; mass spectrometry imaging; nab-paclitaxel; nanoparticles; peritoneal carcinomatosis