α-Tocopherol succinate-modified chitosan as a micellar delivery system for paclitaxel: Preparation, characterization and in vitro/in vivo evaluations

Liang, Na; Sun, Song Yung; Li, Xuefeng; Piao, Hongze; Piao, Hongyu; Cui, Fude; Fang, Liang

doi:10.1016/j.ijpharm.2011.12.004

Cited by 83 publications

(41 citation statements)

References 31 publications

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“…A relatively high surface charge may present a repelling force between the particles and then increase the stability of the solution. 37 In this study, the positive zeta potential of the micelles was attributed to the presence of ionized amino groups on the glycol chitosan backbone.…”

Section: Characterization Of Chgc Micellesmentioning

confidence: 72%

Fabrication and characterization of nuclear localization signal-conjugated glycol chitosan micelles for improving the nuclear delivery of doxorubicin

Yu¹,

Xie²,

Zheng³

et al. 2012

IJN

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Background: Supramolecular micelles as drug-delivery vehicles are generally unable to enter the nucleus of nondividing cells. In the work reported here, nuclear localization signal (NLS)-modified polymeric micelles were studied with the aim of improving nuclear drug delivery. Methods: In this research, cholesterol-modified glycol chitosan (CHGC) was synthesized. NLSconjugated CHGC (NCHGC) was synthesized and characterized using proton nuclear magnetic resonance spectroscopy, dynamic light scattering, and fluorescence spectroscopy. Doxorubicin (DOX), an anticancer drug with an intracellular site of action in the nucleus, was chosen as a model drug. DOX-loaded micelles were prepared by an emulsion/solvent evaporation method. The cellular uptake of different DOX formulations was analyzed by flow cytometry and confocal laser scanning microscopy. The cytotoxicity of blank micelles, free DOX, and DOX-loaded micelles in vitro was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in HeLa and HepG2 cells. Results: The degree of substitution was 5.9 cholesterol and 3.8 NLS groups per 100 sugar residues of the NCHGC conjugate. The critical aggregation concentration of the NCHGC micelles in aqueous solution was 0.0209 mg/mL. The DOX-loaded NCHGC (DNCHGC) micelles were observed as being almost spherical in shape under transmission electron microscopy, and the size was determined as 248 nm by dynamic light scattering. The DOX-loading content of the DNCHGC micelles was 10.1%. The DOX-loaded micelles showed slow drug-release behavior within 72 hours in vitro. The DNCHGC micelles exhibited greater cellular uptake and higher amounts of DOX in the nuclei of HeLa cells than free DOX and DOX-loaded CHGC (DCHGC) micelles. The half maximal inhibitory concentration (IC 50 ) values of free DOX, DCHGC, and DNCHGC micelles against HepG2 cells were 4.063, 0.591, and 0.171 µg/mL, respectively. Moreover, the IC 50 values of free DOX (3.210 µg/mL) and the DCHGC micelles (1.413 µg/mL) against HeLa cells were nearly 6.96-and 3.07-fold (P , 0.01), respectively, higher than the IC 50 value of the DNCHGC micelles (0.461 µg/mL). Conclusion:The results of this study suggest that novel NCHGC micelles could be a potential carrier for nucleus-targeting delivery.

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Section: Characterization Of Chgc Micellesmentioning

confidence: 72%

Fabrication and characterization of nuclear localization signal-conjugated glycol chitosan micelles for improving the nuclear delivery of doxorubicin

Yu¹,

Xie²,

Zheng³

et al. 2012

IJN

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“…The grafted polymers were synthesized following a modified procedure reported by our group previously (Liang et al, 2012). Briefly, a-TPS were dissolved in DMSO and equal amount (1.5 equivalents of a-TPS) of EDC and NHS were added to activate the carboxyl group.…”

Section: Synthesis Of N-tocopheryl-e-pll (Tp-g-pll)mentioning

confidence: 99%

Polymeric lipid vesicles with pH-responsive turning on–off membrane for programed delivery of insulin in GI tract

Fang

Xue

et al. 2016

Drug Delivery

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A kind of polymeric lipid vesicles (PLVs) with pH-responsive turning on-off membrane for programed delivery of insulin in gastrointestinal (GI) tract was developed, which was selfassembled from the grafted amphipathic polymer of N-tocopheryl-N 0 -succinyl-e-poly-L-lysine (TP/SC-g-PLL). By controlling the grafting ratio of hydrophobic alkane and ionizable carboxyl branches, the permeability of membrane was adjustable and thus allowing insulin release in a GI-pH dependent manner. The effects of grafting degree of substitution (DS) on the pHresponsive behavior of the formed vesicles were confirmed by critical aggregation concentration determination, morphology and size characterization. Their transepithelial permeability across the GI tract was proved by both confocal visualization in vitro model of Caco-2 cellular monolayer and in vivo hypoglycemic study in diabetic rats. Accordingly, the work described here indicated that the self-assembled PLVs could be a promising candidate for improving the GI delivery of hydrophilic biomacromolecule agents.

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“…The CS-TOS and PTX-loaded CS-TOS micelles were prepared by the methods as described earlier (Liang et al, 2012). Firstly, the CS-TOS was synthesized by the coupling reaction of carboxyl group of a-tocopherol succinate (TOS) with amino group of chitosan (CS).…”

Section: Preparation Of Ptx-loaded Cs-tos Micellesmentioning

confidence: 99%

“…The PTX-loaded micelles exhibited small particle size and narrow size distribution, high drugloading capacity, good compatibility with blood, and comparable cytotoxicity with Taxol (Liang et al, 2012). It can be considered as a potential injectable delivery system for PTX.…”

Section: Introductionmentioning

confidence: 98%

In vivo pharmacokinetics, biodistribution and antitumor effect of paclitaxel-loaded micelles based on α-tocopherol succinate-modified chitosan

et al. 2015

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In our previous study, a-tocopherol succinate modified chitosan (CS-TOS) was synthesized and encapsulated paclitaxel (PTX) to form micelles. Preliminary study revealed that the CS-TOS was a potential micellar carrier for PTX. In this study, some further researches were done using Taxol formulation as the control to evaluate the micelle system deeply. In vitro cell experiments demonstrated that the cytotoxic effect of PTX-loaded CS-TOS micelles against MCF-7 cells was comparable with that of Taxol formulation, and the PTX-loaded micelles had excellent cellular uptake ability, which was in a time-dependent manner. The in vivo pharmacokinetic study in rats showed that the micelles prolonged the half-life and increased AUC of PTX than Taxol formulation. From biodistribution study, it was clear that for micelles, the drug concentrations in the liver and spleen were significantly higher than those of Taxol formulation, but much lower in the heart and kidney. Furthermore, the PTX-loaded micelles showed superior antitumor effect, but yielded less toxicity as indicated by the results of antitumor efficacy study and survival study in U14 tumor-bearing mice. These results suggested that CS-TOS micelles could be a potentially useful drug delivery system to improve the performance and safety of PTX.

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α-Tocopherol succinate-modified chitosan as a micellar delivery system for paclitaxel: Preparation, characterization and in vitro/in vivo evaluations

Cited by 83 publications

References 31 publications

Fabrication and characterization of nuclear localization signal-conjugated glycol chitosan micelles for improving the nuclear delivery of doxorubicin

Fabrication and characterization of nuclear localization signal-conjugated glycol chitosan micelles for improving the nuclear delivery of doxorubicin

Polymeric lipid vesicles with pH-responsive turning on–off membrane for programed delivery of insulin in GI tract

In vivo pharmacokinetics, biodistribution and antitumor effect of paclitaxel-loaded micelles based on α-tocopherol succinate-modified chitosan

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