Anti-tumoral effect of doxorubicin-loaded poly(vinyl alcohol)/poly(vinyl acetate) microspheres in a rat model

Porous and degradable poly(vinyl alcohol)/poly(vinyl acetate) microspheres (PVA/PVAc-Ms) were synthesized with a diameter in the range of 20-55 mu m by suspension polymerization method suitable for loading and releasing doxorubicin (DOX). In addition, the biological efficacy in vitro of PVA/PVAc-Ms and their anti-tumoral effect in vivo in a rat model were evaluated. The size distribution and morphology of PVA/PVAc-Ms were assessed by microscopy. In vitro degradability was tested according to ISO 10993-13. DOX loading and DOX release were quantified by a multi-mode reader. The biological efficacy in vitro was assessed by cell viability quantification. The anti-tumoral effect in vivo was assessed in a subcutaneous tumor model in rats that received an intra-tumoral injection of PVA/PVAc-Ms: empty Ms in group 1 (n = 16) or DOX (2000 mu g/mL)-loaded Ms in group 2 (n = 16). The mean tumor volume was calculated and samples were processed for histopathological analysis. PVA/PVAc-Ms exhibited a porous surface, a spherical morphology and a diameter in the range of 20-55 mu m. The in vitro degradability was 30% in 38 days. From DOX concentrations of 333 and 2000 mu g/mL, Ms loaded 40% and 21% and released 1.5% and 0.6%, respectively. Cell viability was reduced with DOX loaded PVA/PVAc-Ms. The mean tumor volume was 167.7 +/- 77.6 mm(3) in group 1 and 96.2 +/- 58.2 mm(3) in group 2 (P = 0.0061). The mean percentage value of necrotic areas was 37% in group 1 and 45% in group 2 (no significancy). In conclusion, porous PVA/PVAc-Ms synthesized can load and release DOX, reduce cell viability in vitro and produce an anti-tumoral effect in vivo. [Graphics] .