Using embossing ice particulate method to prepare polyvinyl alcohol/pullulan hydrogels with surface open pores loaded with microspheres for breast cancer treatment

Abstract

In the post-operative treatment of breast cancer, early prevention of locoregional recurrence is crucial to avoid metastasis of cells from leftover microtumor tissues. The limitations in conventional drug delivery systems show a growing clinical demand for disease-specific drug-releasing systems. This study explores a novel poly(vinyl alcohol)/pullulan (PVA/PUL) hydrogel system for local drug delivery in post-operative breast cancer treatment. Hydrogel was produced by combination of lyophilization and embossing ice particulate techniques to create microspheres loaded open pores on the hydrogel surface for localized release of doxorubicin-loaded polycaprolactone microspheres (DOX-PCL-MSs). PVA/PUL hydrogel was successfully crosslinked with glutaraldehyde and stabilized hydrogel structure has possessed slow degradation rate and increasing water retention through 12 days. Release of DOX after 7 and 16 days from DOX-PCL-MSs loaded hydrogels were slower with a 6.2 ± 8.9 % and 56.6 ± 4.5 % release compared to 60.9 ± 14.6 % and 76.8 ± 19.7 % release from free DOX loaded hydrogel since DOX release was controlled by PCL microspheres. When interacted with human breast cancer cell line (MCF-7), DOX-PCL-MSs were able to disrupt cell and spheroid morphology after 7 days at concentrations as low as 12 μg/mL loaded DOX. In vitro cytotoxicity study has showed that, DOX-PCL-MSs loaded hydrogel was able to decrease MCF-7 viability after 7 days of incubation with controlled release of DOX. While free DOX releasing hydrogel has lost cytotoxic activity even after 4 days of incubation. Furthermore, ability of PVA/PUL hydrogel to support L929 cell attachment was shown in the study, suggesting hydrogels potential for promoting tissue regeneration after anti-cancer treatment. The study reveals that PVA/PUL hybrid hydrogels loaded with DOX-PCL-MSs has impactful potential in post-surgical treatment of breast cancer.