Enhanced antitumor efficiency of docetaxel-loaded nanoparticles in a human ovarian xenograft model with lower systemic toxicities by intratumoral delivery

Abstract

Abstract. 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 docetaxelloaded 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.

Cationic PEGylated polycaprolactone nanoparticles carrying post-operation docetaxel for glioma treatment

“…In the literature, the encapsulation efficacy for PCL nanoparticles was found to be between 65−71% [60,70] and for mePEG-PCL nanoparticles to be 80−90% [56,58]. According to our results, the encapsulation efficacy of mePEG-PCL nanoparticles was not found to be as high as reported in the literature.…”

“…As seen in Fig. 5, DOC was completely released from all nanoparticles within 1 h. The PCL nanoparticles are generally expected to give a longer release time due to slower degradation time of PCL [56,58,60] if the drug is entrapped in a nanoparticle matrix. In our study, it is suggested by the encapsulation data shown in Fig.…”

“…The encapsulation efficacy of PCL and mePEG-PCL nanoparticles is not significantly different from one other ( p > 0.05) but CS-coated mePEG-PCL nanoparticles have the largest encapsulation efficacy ( p < 0.05). The mePEG-PCL polymer is more hydrophilic than PCL, as previously mentioned, and this property may be effective for the high encapsulation efficacy as well as smaller particle size as shown in the literature [56,58]. …”

“…In the literature, mePEG-PCL nanoparticles prepared by nanoprecipitation have been found to be generally smaller than 120 nm [53,56–58]; however, PCL nanoparticles prepared by the same technique are between 200–300 nm [55,59]. mePEG-PCL can be solubilized in organic solvents more easily, thanks to the hydrophilic PEG chains as compared to PCL.…”