Study on docetaxel-loaded nanoparticles with high antitumor efficacy against malignant melanoma

Zheng, Donghui; Li, Xin; Xu, Huae; Lu, Xiaowei; Hu, Yong; Fan, Wei

doi:10.1093/abbs/gmp045

Cited by 57 publications

(38 citation statements)

References 31 publications

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“…In order to improve the aqueous solubility of DTX, the commercial preparation Taxotere contains a high concentration of the nonionic surfactant Tween 80 (polysorbate 80), 5 which unfortunately leads to serious side effects, such as hypersensitivity, nephrotoxicity, neurotoxicity, and incompatibility with common polyvinyl chloride intravenous administration sets. 6 In previous reports, various drug delivery systems have been developed to replace the Tween 80-based vehicle for overcoming the aforementioned limitation, including an HP-β-cyclodextrin inclusion complex, 7 nanoparticles, 8 liposomes, 9 and microemulsions. 10 Among these delivery systems being applied to DTX, polymeric micelles are considered one of the strongest potential alternatives since several micellar formulations have been under clinical evaluation as carriers for anticancer drugs.…”

Section: Introductionmentioning

confidence: 99%

Pluronic P105/F127 mixed micelles for the delivery of docetaxel against Taxol-resistant non-small cell lung cancer: optimization and in vitro, in vivo evaluation

Chen¹,

Sha²,

Jiang³

et al. 2013

IJN

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Abstract:The aim of this work was to establish a novel polymeric mixed micelle composed of Pluronic P105 and F127 copolymers loaded with the poorly soluble antitumor drug docetaxel (DTX) against Taxol-resistant non-small cell lung cancer. A central composite design was utilized to optimize the preparation process, helping to improve drug solubilization efficiency and micelle stability. Prepared by a thin-film hydration method, the average size of the optimized mixed micelle was 23 nm, with a 92.40% encapsulation ratio and a 1.81% drug-loading efficiency. The optimized formulation showed high storage stability in lyophilized form, with 95.7% of the drug content remaining after 6 months' storage at 4°C. The in vitro cytotoxicity assay showed that the IC50 values for Taxotere ® and mixed micelles were similar for A549, while on A549/Taxol cell lines, DTX-loaded P105/F127 mixed micelles showed a superior hypersensitizing effect; their IC50 value (0.059 µg/mL) was greatly reduced compared to those of Taxotere injections (0.593 µg/mL). The in vivo pharmacokinetic study showed that the mixed-micelle formulation achieved a 1.85-fold longer mean residence time in circulation and a 3.82-fold larger area under the plasma concentration-time curve than Taxotere. In addition, therapeutic improvement of mixed micelles in vivo against A549/Taxol was obtained. The tumor inhibition rate of the micelles was 69.05%, versus 34.43% for Taxotere (P , 0.01). Therefore, it could be concluded from the results that DTX-loaded P105/F127 mixed micelles might serve as a potential antitumor drug delivery system to overcome multidrug resistance in lung cancer.

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Section: Introductionmentioning

confidence: 99%

Pluronic P105/F127 mixed micelles for the delivery of docetaxel against Taxol-resistant non-small cell lung cancer: optimization and in vitro, in vivo evaluation

Chen¹,

Sha²,

Jiang³

et al. 2013

IJN

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“…To overcome this problem, we evaluated the anticancer efficiency of drug loaded nanoparticles by intratumoral delivery in our previous reports. Cisplatin and Doc was used as model drugs incorporated into nanoparticles formed by amphilic copolymers, demonstrating exciting in vivo anticancer efficacy (14,22). Compared with free drugs, nanoparticle-based drug delivery systems are characterized by the controlled release of incorporated drugs, which may overcome the deficiency of necessary drug retention in the tumor and may reach a satisfying outcome in improving antitumor efficacy when combined with intratumoral delivery instead of intravenous route.…”

Section: Introductionmentioning

confidence: 99%

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

Zheng

Li²,

Lu³

et al. 2010

Oncol Rep

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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.

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“…The analysis of body weight variations could be partially used to define the adverse effects of the different therapy regiments. 37 Therefore, pLNS and tLNS generated less toxicity to mice than Duopafei when administered intravenously under the present experiment condition, which will facilitate its future clinical application. Moreover, it was observed that the mice of the Duopafei group were in a weak state and moved slowly; three of these mice died during the experiment, whereas no obvious alteration was observed in the pLNS and tLNS group.…”

Section: Dtx Concentration (µM) Cell Viability (%)mentioning

confidence: 73%

Folate-targeted docetaxel-lipid-based-nanosuspensions for active-targeted cancer therapy

Wang¹,

Li²,

Zhang³

2012

IJN

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Abstract:The purpose of this study was to develop two novel drug delivery systems based on biodegradable docetaxel-lipid-based-nanosuspensions. The first one was poly(ethylene glycol)-modified docetaxel-lipid-based-nanosuspensions (pLNS). It was developed to increase the cycle time of the drug within the body and enhance the accumulation of the drug at the tumor site. The second one was targeted docetaxel-lipid-based-nanosuspensions (tLNS) using folate as the target ligand. The tLNS could target the tumor cells that overexpressed folate receptor (FR). The morphology, particle size, and zeta potential of pLNS and tLNS were characterized, respectively. The in vitro cytotoxicity evaluation of Duopafei ® , pLNS, and tLNS were performed in human hepatocellular liver carcinoma HepG2 (FR-) and B16 (FR+) cells, respectively. The in vivo antitumor efficacy and pharmacokinetics, as well as the drug tissue distribution, were evaluated in Kunming mice bearing B16 cells. The particle size of pLNS was 204.2 ± 6.18 nm and tLNS had a mean particle size of 220.6 ± 9.54 nm. Cytotoxicity of tLNS against B16 (FR+) cell lines was superior to pLNS (P , 0.05), while there was no significant difference in the half maximum inhibitory concentration values for HepG2 (FR-) cells between pLNS and tLNS. The results of the in vivo antitumor efficacy evaluation showed that tLNS exhibited higher antitumor efficacy by reducing tumor volume (P , 0.01) compared with Duopafei and pLNS, respectively. The results of the in vivo biodistribution study indicate that the better antitumor efficacy of tLNS was attributed to the increased accumulation of the drug in the tumor.

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Study on docetaxel-loaded nanoparticles with high antitumor efficacy against malignant melanoma

Cited by 57 publications

References 31 publications

Pluronic P105/F127 mixed micelles for the delivery of docetaxel against Taxol-resistant non-small cell lung cancer: optimization and in vitro, in vivo evaluation

Pluronic P105/F127 mixed micelles for the delivery of docetaxel against Taxol-resistant non-small cell lung cancer: optimization and in vitro, in vivo evaluation

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

Folate-targeted docetaxel-lipid-based-nanosuspensions for active-targeted cancer therapy

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