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Programmed Hydrolysis in Designing Paclitaxel Prodrug for Nanocarrier Assembly.

Fu Q, Wang Y, Ma Y, Zhang D, Fallon JK, Yang X, Liu D, He Z, Liu F - Sci Rep (2015)

Bottom Line: Nanocarriers delivering prodrugs are a way of improving in vivo effectiveness and efficiency.It was demonstrated in vitro that the hydrolysis of PTX-S-S-VE was enhanced and the cytotoxicity was increased.The present result suggests a new way, use of reduction, to improve the in vivo anticancer activity of a prodrug for nanocarrier delivery by unshielding the ester bond and taking off the steric block.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.

ABSTRACT
Nanocarriers delivering prodrugs are a way of improving in vivo effectiveness and efficiency. For therapeutic efficacy, the prodrug must hydrolyze to its parent drug after administration. Based on the fact that the hydrolysis is impeded by steric hindrance and improved by sufficient polarity, in this study, we proposed the PTX-S-S-VE, the conjugation of paclitaxel (PTX) to vitamin E (VE) through a disulfide bridge. This conjugate possessed the following advantages: first, it can be encapsulated in the VE/VE2-PEG2000/water nanoemulsions because of favorable hydrophobic interactions; second, the nanoemulsions had a long blood circulation time; finally, the concentrated glutathione in the tumor microenvironment could cleave the disulfide bond to weaken the steric hindrance and increase the polarity, promoting the hydrolysis to PTX and increasing the anticancer activity. It was demonstrated in vitro that the hydrolysis of PTX-S-S-VE was enhanced and the cytotoxicity was increased. In addition, PTX-S-S-VE had greater anticancer activity against the KB-3-1 cell line tumor xenograft and the tumor size was smaller after the 4(th) injection. The present result suggests a new way, use of reduction, to improve the in vivo anticancer activity of a prodrug for nanocarrier delivery by unshielding the ester bond and taking off the steric block.

No MeSH data available.


Related in: MedlinePlus

TEM images of PTX-VE/VE/VE2-PEG2000/water (a) and PTX-S-S-VE/VE/VE2-PEG2000/water (b) NES.
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f5: TEM images of PTX-VE/VE/VE2-PEG2000/water (a) and PTX-S-S-VE/VE/VE2-PEG2000/water (b) NES.

Mentions: PTX-VE/VE/VE2-PEG2000 NES has been prepared because of favorable affinity for PTX-VE, VE, and VE2-PEG2000. In this study, PTX-S-S-VE/VE/VE2-PEG2000 NES was also prepared successfully. The particle size, zeta potential, and morphology were characterized. As shown in Fig. 5, for both NES, the particles were of similar spherical shape and size (100–150 nm). Consistent with the TEM images, the dynamic light scattering results showed that both NES were about 130 nm (Table 1, and Figure S8–9). The small PDI indicated that the particles were of a narrow size range. It was demonstrated that the PTX-S-S-VE/VE/VE2-PEG2000 NES was physically stable for at least 12 months (Table S1). Therefore, the PTX-S-S-VE/VE/VE2-PEG2000 NES was suitable for in vivo studies.


Programmed Hydrolysis in Designing Paclitaxel Prodrug for Nanocarrier Assembly.

Fu Q, Wang Y, Ma Y, Zhang D, Fallon JK, Yang X, Liu D, He Z, Liu F - Sci Rep (2015)

TEM images of PTX-VE/VE/VE2-PEG2000/water (a) and PTX-S-S-VE/VE/VE2-PEG2000/water (b) NES.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4499798&req=5

f5: TEM images of PTX-VE/VE/VE2-PEG2000/water (a) and PTX-S-S-VE/VE/VE2-PEG2000/water (b) NES.
Mentions: PTX-VE/VE/VE2-PEG2000 NES has been prepared because of favorable affinity for PTX-VE, VE, and VE2-PEG2000. In this study, PTX-S-S-VE/VE/VE2-PEG2000 NES was also prepared successfully. The particle size, zeta potential, and morphology were characterized. As shown in Fig. 5, for both NES, the particles were of similar spherical shape and size (100–150 nm). Consistent with the TEM images, the dynamic light scattering results showed that both NES were about 130 nm (Table 1, and Figure S8–9). The small PDI indicated that the particles were of a narrow size range. It was demonstrated that the PTX-S-S-VE/VE/VE2-PEG2000 NES was physically stable for at least 12 months (Table S1). Therefore, the PTX-S-S-VE/VE/VE2-PEG2000 NES was suitable for in vivo studies.

Bottom Line: Nanocarriers delivering prodrugs are a way of improving in vivo effectiveness and efficiency.It was demonstrated in vitro that the hydrolysis of PTX-S-S-VE was enhanced and the cytotoxicity was increased.The present result suggests a new way, use of reduction, to improve the in vivo anticancer activity of a prodrug for nanocarrier delivery by unshielding the ester bond and taking off the steric block.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.

ABSTRACT
Nanocarriers delivering prodrugs are a way of improving in vivo effectiveness and efficiency. For therapeutic efficacy, the prodrug must hydrolyze to its parent drug after administration. Based on the fact that the hydrolysis is impeded by steric hindrance and improved by sufficient polarity, in this study, we proposed the PTX-S-S-VE, the conjugation of paclitaxel (PTX) to vitamin E (VE) through a disulfide bridge. This conjugate possessed the following advantages: first, it can be encapsulated in the VE/VE2-PEG2000/water nanoemulsions because of favorable hydrophobic interactions; second, the nanoemulsions had a long blood circulation time; finally, the concentrated glutathione in the tumor microenvironment could cleave the disulfide bond to weaken the steric hindrance and increase the polarity, promoting the hydrolysis to PTX and increasing the anticancer activity. It was demonstrated in vitro that the hydrolysis of PTX-S-S-VE was enhanced and the cytotoxicity was increased. In addition, PTX-S-S-VE had greater anticancer activity against the KB-3-1 cell line tumor xenograft and the tumor size was smaller after the 4(th) injection. The present result suggests a new way, use of reduction, to improve the in vivo anticancer activity of a prodrug for nanocarrier delivery by unshielding the ester bond and taking off the steric block.

No MeSH data available.


Related in: MedlinePlus