Docetaxel load biodegradable porous microspheres for the treatment of colorectal peritoneal carcinomatosis.
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<0.05). Thus, our results suggested that DOC MS may have great potential applications in clinic.
State Key Laboratory of Biotherapy and Cancer Center, and Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, PR China.
RangRang
R
Fan
State Key Laboratory of Biotherapy and Cancer Center, and Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, PR China.
YueLong
Y
Wang
Key Laboratory of Xinjiang Phytomedicine Resources, Shihezi 832002, PR China.
Bo
B
Han
State Key Laboratory of Biotherapy and Cancer Center, and Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, PR China. Electronic address: luo_youfu@scu.edu.cn.
YouFu
Y
Luo
State Key Laboratory of Biotherapy and Cancer Center, and Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, PR China.
LiangXue
L
Zhou
State Key Laboratory of Biotherapy and Cancer Center, and Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, PR China.
XiRui
X
Peng
State Key Laboratory of Biotherapy and Cancer Center, and Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, PR China.
Min
M
Wu
State Key Laboratory of Biotherapy and Cancer Center, and Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, PR China.
Yu
Y
Zheng
State Key Laboratory of Biotherapy and Cancer Center, and Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, PR China. Electronic address: guogang@scu.edu.cn.
Gang
G
Guo
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000473:pathology*; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D051379:Mice; D008863:Microspheres; D010316:Particle Size; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D020442:Poloxamer / Q000737:chemistry; D016062:Porosity; D043823:Taxoids / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D004337:Drug Carriers; D043823:Taxoids; D020442:Poloxamer; D000077143:Docetaxel; D019344:Lactic Acid
Colorectal peritoneal carcinomatosis; PLLA–L121–PLLA; Porous microspheres