Docetaxel load biodegradable porous microspheres for the treatment of colorectal peritoneal carcinomatosis.

Abstract Micro- and nanoparticle formulations are widely used to improve the bioavailability of low solubility drugs. In this study, biodegradable poly(L-lactide acid)–Pluronic L121–poly(L-lactide acid) (PLLA–L121–PLLA) was developed. And then a controlled drug delivery system (CDDS), docetaxel (DOC) loaded PLLA–L121–PLLA porous microsphere (DOC MS) was prepared for colorectal peritoneal carcinomatosis (CRPC) therapy. DOC MS was prepared by DOC and PLLA–L121–PLLA using an oil-in-water emulsion solvent evaporation method. The particle size, morphological characteristics, encapsulation efficiency, in vitro drug release studies and in vitro cytotoxicity of DOC MS have been investigated. In vitro release profile demonstrated a significant difference between rapid release of free DOC and much slower and sustained release of DOC MS. Furthermore, cytotoxicity assay indicated cytotoxicity was increased after DOC was encapsulated into polymeric microspheres. In addition, intraperitoneal administration of DOC MS could effectively suppress growth and metastasis of CT26 peritoneal carcinomatosis in vivo , and prolonged the survival of tumor bearing mice. Immunohistochemistry staining of tumor tissues with Ki-67 revealed that DOC MS induced a stronger anti-tumor effect by increasing apoptosis of tumor cells in contrast to other groups ( P