Enhanced antitumor efficiency of docetaxel-loaded nanoparticles in a human ovarian xenograft model with lower systemic toxicities by intratumoral delivery.
As successful chemotherapy with the taxanes needs to reduce the toxic side effects against normal tissues and avoid the detrimental effects caused by intolerable solvents, drug delivery system using soluble polymeric micelles tends to be the focus. Docetaxel (Doc) has demonstrated extraordinary activities against a variety of solid tumors. However, the clinical efficacy is contrasted by its toxicity profile. To reduce the toxicity and enhance the circulation time of Doc, core-shell structure nanoparticles were prepared from block copolymer of methoxy poly(ethylene glycol)-polycaprolactone (mPEG-PCL). It was found that Doc can be incorporated into the nanoparticles with high encapsulation efficiency of more than 90%. In vitro release study showed that Doc was released from Doc-np in a sustained manner. In vitro cytotoxicity studies indicated that IC50 of docetaxel-loaded nanoparticles (Doc-np) against SKOV3 cells is significantly lower than that of free Doc. Furthermore, intratumoral administration was applied to improve the tumor-targeted delivery in the in vivo evaluation. Compared with free Doc, Doc-np exhibited superior antitumor effect by delaying tumor growth when delivered intratumorally. Blood test, as well as liver and kidney function, showed that Doc-np had little toxicity while free Doc induce severe anemia and liver damage. These results suggest that Doc-np are effective in inhibiting the growth of human ovarian cancer with little toxicity to normal tissues, and intratumoral delivery of Doc-np could be a clinically useful therapeutic regimen and merit more research to evaluate the feasibility of clinical application.
Zheng
Donghui
D
Department of Nephrology, Huai'an Hospital Affiliated to Xuzhou Medical College and Huai'an Second Hospital, Huai'an 223002, P.R. China.
Li
Dake
D
Lu
Xiaowei
X
Feng
Zhenqing
Z
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D000077143:Docetaxel; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage*; D010051:Ovarian Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage* / Q000633:toxicity; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel