Andrea Salis1, Elena P Porcu2, Elisabetta Gavini1, Giulia R Fois3, Antonia Icaro Cornaglia4, Giovanna Rassu1, Marco Diana3, Marcello Maestri5, Paolo Giunchedi1, Ioannis Nikolakakis6. 1. a Department of Chemistry and Pharmacy , University of Sassari , Sassari , Italy. 2. b Department of Diagnostic, Pediatric, Clinical and Surgical Science , University of Pavia , Pavia , Italy. 3. c 'G. Minardi' Laboratory of Cognitive Neuroscience, Department of Chemistry and Pharmacy , University of Sassari , Sassari , Italy. 4. d Department of Public Health, Experimental and Forensic Medicine, Unit of Histology , University of Pavia , Pavia , Italy. 5. e Surgery 1, IRCCS Policlinico San Matteo Foundation and Department of Diagnostic, Pediatric, Clinical and Surgical Sciences , University of Pavia , Pavia , Italy. 6. f Department of Pharmaceutical Technology, School of Pharmacy, Faculty of Health Sciences , Aristotle University of Thessaloniki , Thessaloniki , Greece.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: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.
Entities:
Keywords:
In situ forming microspheres; hepatocellular carcinoma; mixture experimental design; poly(ε-caprolactone); post embolization syndrome; transarterial embolization