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Antitumor activity of docetaxel-loaded polymeric nanoparticles fabricated by Shirasu porous glass membrane-emulsification technique.

Yu Y, Tan S, Zhao S, Zhuang X, Song Q, Wang Y, Zhou Q, Zhang Z - Int J Nanomedicine (2013)

Bottom Line: Previously, we synthesized a novel copolymer, poly(lactide)-D-α-tocopheryl polyethylene glycol 1000 succinate (PLA-TPGS), and found that it exhibited great potential in drug delivery with improved properties.The tumor-inhibitory effect of DTX-loaded nanoparticles was observed in vivo in an H22 tumor-bearing mice model via intravenous administration.This indicated that PLA-TPGS nanoparticles are a feasible drug-delivery formulation with a pilot fabrication technique and have superior pharmacokinetic and anticancer effects compared to the commercially available Taxotere.

View Article: PubMed Central - PubMed

Affiliation: Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, People’s Republic of China.

ABSTRACT
Docetaxel (DTX) has excellent efficiency against a wide spectrum of cancers. However, the current clinical formulation has limited its usage, as it causes some severe side effects. Various polymeric nanoparticles have thus been developed as alternative formulations of DTX, but they have been mostly fabricated on a laboratory scale. Previously, we synthesized a novel copolymer, poly(lactide)-D-α-tocopheryl polyethylene glycol 1000 succinate (PLA-TPGS), and found that it exhibited great potential in drug delivery with improved properties. In this study, we applied the Shirasu porous glass (SPG) membrane-emulsification technique to prepare the DTX-loaded PLA-TPGS nanoparticles on a pilot scale. The effect of several formulation variables on the DTX-loaded nanoparticle properties, including particle size, zeta potential, and drug-encapsulation efficiency, were investigated based on surfactant type and concentration in the aqueous phase, organic/aqueous phase volumetric ratio, membrane-pore size, transmembrane cycles, and operation pressure. The DTX-loaded nanoparticles were obtained with sizes of 306.8 ± 5.5 nm and 334.1 ± 2.7 nm (mean value ± standard deviation), and drug-encapsulation efficiency of 81.8% ± 4.5% and 64.5% ± 2.7% for PLA-TPGS and poly(lactic-co-glycolic acid) (PLGA) nanoparticles, respectively. In vivo pharmacokinetic study exhibited a significant advantage of PLA-TPGS nanoparticles over PLGA nanoparticles and Taxotere. Drug-loaded PLA-TPGS nanoparticles exhibited 1.78-, 6.34- and 3.35-fold higher values for area under the curve, half-life, and mean residence time, respectively, compared with those of PLGA nanoparticles, and 2.23-, 13.2-, 8.51-fold higher than those of Taxotere, respectively. In vivo real-time distribution of nanoparticles was measured on tumor-bearing mice by near-infrared fluorescence imaging, which demonstrated that the PLA-TPGS nanoparticles achieved much higher concentration and longer retention in tumors than PLGA nanoparticles after intravenous injection. This is consistent with the pharmacokinetic behavior of the nanoparticles. The tumor-inhibitory effect of DTX-loaded nanoparticles was observed in vivo in an H22 tumor-bearing mice model via intravenous administration. This indicated that PLA-TPGS nanoparticles are a feasible drug-delivery formulation with a pilot fabrication technique and have superior pharmacokinetic and anticancer effects compared to the commercially available Taxotere.

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(A–C) In vivo antitumor efficiency of Taxotere and docetaxel-loaded poly(lactic-co-glycolic acid) (PLGA) and poly(lactide)-D-α-tocopheryl polyethylene glycol 1000 succinate (PLA-TPGS) nanoparticles (n = 7). (A) Weight changes of tumor-bearing mice; (B) survival rate of H22-bearing mice; (C) relative tumor-growth ratio (*P < 0.05, **P < 0.01).Abbreviation: NPs, nanoparticles.
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f9-ijn-8-2641: (A–C) In vivo antitumor efficiency of Taxotere and docetaxel-loaded poly(lactic-co-glycolic acid) (PLGA) and poly(lactide)-D-α-tocopheryl polyethylene glycol 1000 succinate (PLA-TPGS) nanoparticles (n = 7). (A) Weight changes of tumor-bearing mice; (B) survival rate of H22-bearing mice; (C) relative tumor-growth ratio (*P < 0.05, **P < 0.01).Abbreviation: NPs, nanoparticles.

Mentions: It has been clarified that DTX-loaded PLA-TPGS nanoparticles can prolong the blood circulation time of DTX. The antitumor efficacy of nanoparticles was further explored on H22 cell-bearing mice, as shown in Figure 9. Although all the groups showed tumor inhibition as opposed to the saline control group (at days 2, 3, 4, and 6, P < 0.01 for Taxotere, DTX-loaded PLA-TPGS NPs, and PLGA NPs versus saline), DTX-loaded PLA-TPGS nanoparticles exhibited the best effect on tumor inhibition and safety, with minimal change in body weight during treatment. Taxotere-treated mice exhibited a significant loss in body weight. DTX-loaded PLA-TPGS nanoparticles showed a better effect than that of PLGA nanoparticles on day 9 (P < 0.05). Furthermore, the mean survival rate increased remarkably with DTX-loaded PLA-TPGS nanoparticle treatment compared to that of the DTX-loaded PLGA nanoparticle- and Taxotere-treated groups. These results confirmed that DTX-loaded PLA-TPGS nanoparticles exhibited potential for tumor-growth inhibition. The inhibition is nevertheless not as efficient as previously demonstrated on HT-29 human colon cancers.18 This may be attributed to the fact that DTX is not especially efficient in treating hepatic cancers.39,40 It still demonstrated that DTX-loaded PLA-TPGS nanoparticles can be used in treating hepatic cancer. It was also worth noting that although DTX-loaded PLA-TPGS nanoparticles showed a higher pharmacokinetic property than Taxotere, their tumor-inhibition result was not statistically significant.


Antitumor activity of docetaxel-loaded polymeric nanoparticles fabricated by Shirasu porous glass membrane-emulsification technique.

Yu Y, Tan S, Zhao S, Zhuang X, Song Q, Wang Y, Zhou Q, Zhang Z - Int J Nanomedicine (2013)

(A–C) In vivo antitumor efficiency of Taxotere and docetaxel-loaded poly(lactic-co-glycolic acid) (PLGA) and poly(lactide)-D-α-tocopheryl polyethylene glycol 1000 succinate (PLA-TPGS) nanoparticles (n = 7). (A) Weight changes of tumor-bearing mice; (B) survival rate of H22-bearing mice; (C) relative tumor-growth ratio (*P < 0.05, **P < 0.01).Abbreviation: NPs, nanoparticles.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3735276&req=5

f9-ijn-8-2641: (A–C) In vivo antitumor efficiency of Taxotere and docetaxel-loaded poly(lactic-co-glycolic acid) (PLGA) and poly(lactide)-D-α-tocopheryl polyethylene glycol 1000 succinate (PLA-TPGS) nanoparticles (n = 7). (A) Weight changes of tumor-bearing mice; (B) survival rate of H22-bearing mice; (C) relative tumor-growth ratio (*P < 0.05, **P < 0.01).Abbreviation: NPs, nanoparticles.
Mentions: It has been clarified that DTX-loaded PLA-TPGS nanoparticles can prolong the blood circulation time of DTX. The antitumor efficacy of nanoparticles was further explored on H22 cell-bearing mice, as shown in Figure 9. Although all the groups showed tumor inhibition as opposed to the saline control group (at days 2, 3, 4, and 6, P < 0.01 for Taxotere, DTX-loaded PLA-TPGS NPs, and PLGA NPs versus saline), DTX-loaded PLA-TPGS nanoparticles exhibited the best effect on tumor inhibition and safety, with minimal change in body weight during treatment. Taxotere-treated mice exhibited a significant loss in body weight. DTX-loaded PLA-TPGS nanoparticles showed a better effect than that of PLGA nanoparticles on day 9 (P < 0.05). Furthermore, the mean survival rate increased remarkably with DTX-loaded PLA-TPGS nanoparticle treatment compared to that of the DTX-loaded PLGA nanoparticle- and Taxotere-treated groups. These results confirmed that DTX-loaded PLA-TPGS nanoparticles exhibited potential for tumor-growth inhibition. The inhibition is nevertheless not as efficient as previously demonstrated on HT-29 human colon cancers.18 This may be attributed to the fact that DTX is not especially efficient in treating hepatic cancers.39,40 It still demonstrated that DTX-loaded PLA-TPGS nanoparticles can be used in treating hepatic cancer. It was also worth noting that although DTX-loaded PLA-TPGS nanoparticles showed a higher pharmacokinetic property than Taxotere, their tumor-inhibition result was not statistically significant.

Bottom Line: Previously, we synthesized a novel copolymer, poly(lactide)-D-α-tocopheryl polyethylene glycol 1000 succinate (PLA-TPGS), and found that it exhibited great potential in drug delivery with improved properties.The tumor-inhibitory effect of DTX-loaded nanoparticles was observed in vivo in an H22 tumor-bearing mice model via intravenous administration.This indicated that PLA-TPGS nanoparticles are a feasible drug-delivery formulation with a pilot fabrication technique and have superior pharmacokinetic and anticancer effects compared to the commercially available Taxotere.

View Article: PubMed Central - PubMed

Affiliation: Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, People’s Republic of China.

ABSTRACT
Docetaxel (DTX) has excellent efficiency against a wide spectrum of cancers. However, the current clinical formulation has limited its usage, as it causes some severe side effects. Various polymeric nanoparticles have thus been developed as alternative formulations of DTX, but they have been mostly fabricated on a laboratory scale. Previously, we synthesized a novel copolymer, poly(lactide)-D-α-tocopheryl polyethylene glycol 1000 succinate (PLA-TPGS), and found that it exhibited great potential in drug delivery with improved properties. In this study, we applied the Shirasu porous glass (SPG) membrane-emulsification technique to prepare the DTX-loaded PLA-TPGS nanoparticles on a pilot scale. The effect of several formulation variables on the DTX-loaded nanoparticle properties, including particle size, zeta potential, and drug-encapsulation efficiency, were investigated based on surfactant type and concentration in the aqueous phase, organic/aqueous phase volumetric ratio, membrane-pore size, transmembrane cycles, and operation pressure. The DTX-loaded nanoparticles were obtained with sizes of 306.8 ± 5.5 nm and 334.1 ± 2.7 nm (mean value ± standard deviation), and drug-encapsulation efficiency of 81.8% ± 4.5% and 64.5% ± 2.7% for PLA-TPGS and poly(lactic-co-glycolic acid) (PLGA) nanoparticles, respectively. In vivo pharmacokinetic study exhibited a significant advantage of PLA-TPGS nanoparticles over PLGA nanoparticles and Taxotere. Drug-loaded PLA-TPGS nanoparticles exhibited 1.78-, 6.34- and 3.35-fold higher values for area under the curve, half-life, and mean residence time, respectively, compared with those of PLGA nanoparticles, and 2.23-, 13.2-, 8.51-fold higher than those of Taxotere, respectively. In vivo real-time distribution of nanoparticles was measured on tumor-bearing mice by near-infrared fluorescence imaging, which demonstrated that the PLA-TPGS nanoparticles achieved much higher concentration and longer retention in tumors than PLGA nanoparticles after intravenous injection. This is consistent with the pharmacokinetic behavior of the nanoparticles. The tumor-inhibitory effect of DTX-loaded nanoparticles was observed in vivo in an H22 tumor-bearing mice model via intravenous administration. This indicated that PLA-TPGS nanoparticles are a feasible drug-delivery formulation with a pilot fabrication technique and have superior pharmacokinetic and anticancer effects compared to the commercially available Taxotere.

Show MeSH
Related in: MedlinePlus