title: In situ forming biodegradable poly(ε-caprolactone) microsphere systems: a challenge for transarterial embolization therapy. In vitro and preliminary ex vivo studies.
abstract: In situ forming biodegradable poly(ε-caprolactone) (PCL) microspheres (PCL-ISM) system was developed as a novel embolic agent for transarterial embolization (TAE) therapy of hepatocellular carcinoma (HCC). Ibuprofen sodium (Ibu-Na) was loaded on this platform to evaluate its potential for the treatment of post embolization syndrome.
  
  
  
  The influence of formulation parameters on the size/shape, encapsulation efficiency and drug release was investigated using mixture experimental design. Regression models were derived and used to optimize the formulation for particle size, encapsulation efficiency and drug release profile for TAE therapy. An ex vivo model using isolated rat livers was established to assess the in situ formation of microspheres.
  
  
  
  All PCL-ISM components affected the studied properties and fitting indices of the regression models were high (Radj2= 0.810 for size, 0.964 encapsulation efficiency, and 0.993 or 0.971 for drug release at 30 min or 48 h). The optimized composition was: PCL = 4%, NMP = 43.1%, oil = 48.9%, surfactant = 2% and drug = 2%. Ex vivo studies revealed that PCL-ISM was able to form microspheres in the hepatic arterial bed.
  
  
  
  PCL-ISM system provides a novel tool for the treatment of HCC and post-embolization syndrome. It is capable of forming microspheres with desirable size and Ibu-Na release profile after injection into blood vessels.
authors.affiliation: a Department of Chemistry and Pharmacy , University of Sassari , Sassari , Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Salis
authors.affiliation: b Department of Diagnostic, Pediatric, Clinical and Surgical Science , University of Pavia , Pavia , Italy.
authors.forename: Elena P
authors.initials: EP
authors.lastname: Porcu
authors.affiliation: a Department of Chemistry and Pharmacy , University of Sassari , Sassari , Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Gavini
authors.affiliation: c 'G. Minardi' Laboratory of Cognitive Neuroscience, Department of Chemistry and Pharmacy , University of Sassari , Sassari , Italy.
authors.forename: Giulia R
authors.initials: GR
authors.lastname: Fois
authors.affiliation: d Department of Public Health, Experimental and Forensic Medicine, Unit of Histology , University of Pavia , Pavia , Italy.
authors.forename: Antonia
authors.initials: A
authors.lastname: Icaro Cornaglia
authors.affiliation: a Department of Chemistry and Pharmacy , University of Sassari , Sassari , Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Rassu
authors.affiliation: c 'G. Minardi' Laboratory of Cognitive Neuroscience, Department of Chemistry and Pharmacy , University of Sassari , Sassari , Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Diana
authors.affiliation: e Surgery 1, IRCCS Policlinico San Matteo Foundation and Department of Diagnostic, Pediatric, Clinical and Surgical Sciences , University of Pavia , Pavia , Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Maestri
authors.affiliation: a Department of Chemistry and Pharmacy , University of Sassari , Sassari , Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Giunchedi
authors.affiliation: f Department of Pharmaceutical Technology, School of Pharmacy, Faculty of Health Sciences , Aristotle University of Thessaloniki , Thessaloniki , Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Nikolakakis
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical; D065546:Drug Liberation; D007052:Ibuprofen / Q000008:administration & dosage*; D008297:Male; D008863:Microspheres; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D011091:Polyesters; C016240:polycaprolactone; D007052:Ibuprofen
keywords: In situ forming microspheres; hepatocellular carcinoma; mixture experimental design; poly(ε-caprolactone); post embolization syndrome; transarterial embolization