Enhanced efficiency of thermally targeted taxanes delivery in a human xenograft model of gastric cancer.
Since successful chemotherapy with taxanes requires an improvement in their therapeutic index, especially by the reduction in unwanted systemic toxicity of either drug or adjuvants, we have investigated and are reporting results from an investigation of the use of a novel polymeric thermosensitive micellar delivery system for docetaxel and paclitaxel. Here we reported a novel metastable thermosensitive polymeric micelle for docetaxel and paclitaxel delivery [poly(N-isopropylacrylamide-co-acrylamide)-b-poly(DL-lactide), Poly(IPAAm-co-AAm)-b-PDLLA]. Previous in vitro efficacy studies indicated that, with hyperthermia, docetaxel-loaded micelles showed stronger cytotoxicity to different tumor cell lines than conventional docetaxel formulation while exhibiting slighter toxicity to normal cells. Present in vivo studies indicated that at the same dose level of docetaxel (paclitaxel), hyperthermia greatly enhanced the antitumor effect of micellar docetaxel (paclitaxel) in human gastric BGC mouse xenograft model by showing an extraordinary tumor volume and weight growth percentage inhibition of more than 80%. Meanwhile, acute toxicity tests features the lower LD(50) of the combination of hyperthermia and micellar docetaxel (paclitaxel) compared to that of the control group. The present results suggest that poly(IPAAm-co-AAm)-b-PDLLA micelles could be a clinically useful chemotherapeutic formulation and merit further research to evaluate the feasibility of clinical application.
Liu
Baorui
B
Department of Oncology, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing 210008, P.R. China. baoruiliu@nju.edu.cn
Yang
Mi
M
Li
Xiaolin
X
Qian
Xiaoping
X
Shen
Zetian
Z
Ding
Yitao
Y
Yu
Lixia
L
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D000077143:Docetaxel; D006801:Humans; D007928:Lethal Dose 50; D051379:Mice; D008823:Micelles; D009368:Neoplasm Transplantation; D017239:Paclitaxel / Q000008:administration & dosage* / Q000627:therapeutic use; D013274:Stomach Neoplasms / Q000188:drug therapy*; D043823:Taxoids / Q000008:administration & dosage* / Q000627:therapeutic use
D000972:Antineoplastic Agents, Phytogenic; D008823:Micelles; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel