In situ forming biodegradable poly(ε-caprolactone) microsphere systems: a challenge for transarterial embolization therapy. In vitro and preliminary ex vivo studies

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.