In vitro evaluation on novel modified chitosan for targeted antitumor drug delivery

Qu, Ding; Lin, Haijiao; Zhang, Nan; Xue, Jingwei; Zhang, Can

doi:10.1016/j.carbpol.2012.08.112

Cited by 69 publications

(48 citation statements)

References 41 publications

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“…Recently, polymeric micelles fabricated from natural and synthetic polymers have received particular attention. Polymeric micelles are self-assemblies of amphiphilic block or grafted copolymers forming a core-shell structure in aqueous media and poorly soluble drugs can be solubilized within the hydrophobic inner core of the micelles (Qu et al, 2013). Although micellar systems have made a significant impact on the development of anticancer drug delivery systems, some improvements are still essential.…”

Section: Few Years Ago Abraxanementioning

confidence: 99%

“…Hence, many attempts have been devoted to substitute the Cremophor Õ EL-based formulation with alternative carriers which enable delivering PTX selectively to the tumor tissues with significantly reduced adverse effects on normal cells. Numerous drug delivery systems including parenteral emulsions (He et al, 2003;Nornoo et al, 2008), liposomes (Fetterly et al, 2003;Soenpenberg et al, 2004), nanoparticles (Hawkins et al, 2008;Zhu et al, 2010) and polymeric micelles (Qu et al, 2009;Tao et al, 2012;Qu et al, 2013;Wang et al, 2013) have extensively been studied and evaluated for parenteral delivery of PTX into cancer cells.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

In vivopharmacokinetics, biodistribution and anti-tumor effect of paclitaxel-loaded targeted chitosan-based polymeric micelle

Rezazadeh¹,

Emami²,

Hasanzadeh³

et al. 2014

Drug Delivery

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A water-insoluble anti-tumor agent, paclitaxel (PTX) was successfully incorporated into noveltargeted polymeric micelles based on tocopherol succinate-chitosan-polyethylene glycol-folic acid (PTX/TS-CS-PEG-FA). The aim of the present study was to evaluate the pharmacokinetics, tissue distribution and efficacy of PTX/TS-CS-PEG-FA in comparison to Anzatax Õ in tumor bearing mice. The micellar formulation showed higher in vitro cytotoxicity against mice breast cancer cell line, 4T1, due to the folate receptor-mediated endocytosis. The IC 50 value of PTX, a concentration at which 50% cells are killed, was 1.17 and 0.93 mM for Anzatax Õ and PTX/TS-CS-PEG-FA micelles, respectively. The in vivo anti-tumor efficacy of PTX/TS-CS-PEG-FA, as measured by reduction in tumor volume of 4T1 mouse breast cancer injected in Balb/c mice was significantly greater than that of Anzatax Õ . Pharmacokinetic study in tumor bearing mice revealed that the micellar formulation prolonged the systemic circulation time of PTX and the AUC of PTX/TS-CS-PEG-FA was obtained 0.83-fold lower than Anzatax Õ . Compared with Anzatax Õ , the V d , T 1/2ß and MRT of PTX/TS-CS-PEG-FA was increased by 2.76, 2.05 and 1.68-fold, respectively. As demonstrated by tissue distribution, the PTX/TS-CS-PEG-FA micelles increased accumulation of PTX in tumor, therefore, resulted in anti-tumor effects enhancement and drug concentration in the normal tissues reduction. Taken together, our evaluations show that PTX/TS-CS-PEG-FA micelle is a potential drug delivery system of PTX for the effective treatment of the tumor and systematic toxicity reduction, thus, the micellar formulation can provide a useful alternative dosage form for intravenous administration of PTX. KeywordsBiodistribution, in vivo anti-tumor effect, Paclitaxel, pharmacokinetics, targeted polymeric micelle History

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Section: Few Years Ago Abraxanementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

In vivopharmacokinetics, biodistribution and anti-tumor effect of paclitaxel-loaded targeted chitosan-based polymeric micelle

Rezazadeh¹,

Emami²,

Hasanzadeh³

et al. 2014

Drug Delivery

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show abstract

“…17,18 When the cells grew up to 60% confluence, 200 μL of FBS-free culture medium containing 100 mM galactose, 0.1% NaN 3 , 10 nM NH 4 Cl, 0.8 μM sucrose, 0.2 nM genistein and 0.4 nM amiloride was incubated with the cells for 2 h respectively, which was followed by adding various FITC-labeled formulations in the presence of different inhibitors. After another 2 h, the cells were again treated in the above-mentioned process and analyzed by flow cytometry.…”

Section: Cellular Uptake and Internalization Mechanismmentioning

confidence: 99%

“…24 As shown in Figure 5C, both C-MEs and Gal(oct)-C-MEs produced a significantly enhanced apoptosis effect compared with coix oil-MEs, suggesting that coixan and coix oil were capable of apoptosis induction synergistically using such coix component-based microemulsion. [15][16][17][18] Note that 86.3% of HepG2 cells treated with Gal(oct)-C-MEs induced apoptosis, which was 1.2-fold higher than that in the C-MEs group. These findings indicated that the synergistic anticancer effect by rational drug combination and the improved intracellular accumulation by the rational design of tumor-targeted ligand were of great importance in cell apoptosis induction.…”

Section: Qu Et Almentioning

confidence: 99%

Octanoyl galactose ester-modified microemulsion system self-assembled by coix seed components to enhance tumor targeting and hepatoma therapy

Qu¹,

Liu²,

Huang³

et al. 2017

IJN

Self Cite

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A nanosized drug delivery platform with a combination of rational components and tumor targeting is significant for enhancement of anticancer therapy and reduction of side effects. In this study, we developed a octanoyl galactose ester-modified microemulsion system self-assembled by coix seed components (Gal(oct)-C-MEs), which improved the tumor accumulation through asialoglycoprotein receptor-mediated endocytosis and promoted the antitumor efficacy through multicomponent-mediated synergistic effect. Octanoyl galactose ester (Gal(oct)) with a yield of 82.3% was synthesized through a green enzymatic reaction and multidimensional characterization. Gal(oct)-C-MEs with a spherical shape had a small and uniform particle size (58.49±1.03 nm), narrow polydispersity index (0.09±0.01) and neutral surface charge (−5.82±0.57 mV). In the cellular uptake studies, the internalized Gal(oct)-C-ME was 2.28-fold higher relative to that of coix seed component-based microemulsions (C-MEs). The half-maximal inhibitory concentration of Gal(oct)-C-MEs against HepG2 cells was 46.5±2.4 μg/mL, which was notably higher than that of C-MEs. Importantly, the intratumor fluorescence of HepG2 xenograft-bearing nude mice treated with Cy5/Gal(oct)-C-MEs was 1.9-fold higher relative to treatment with Cy5/C-MEs. In the study of antitumor efficacy in vivo, HepG2 xenograft-bearing nude mice intragastrically administered Gal(oct)-C-MEs for 14 days exhibited the strongest inhibition of tumor growth and the lowest toxicity against liver and kidney among all the treatments. In summary, Gal(oct)-C-ME, as a highly effective and safe anticancer drug delivery system, showed promising potential for hepatoma therapy.

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“…1,[6][7][8] However, the severe unwanted effects resulting from chemotherapeutic agents cannot be ignored, especially immunosuppression and gastrointestinal responses. 9,10 Recent studies have explored several useful approaches to alleviating side effects and enhancing the extent of tumor cell killing by moderating the rate of drug exposure during treatment.…”

mentioning

confidence: 99%

Microemulsion-based synergistic dual-drug codelivery system for enhanced apoptosis of tumor cells

Qu¹,

Ma²,

Sun³

et al. 2015

IJN

Self Cite

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A microemulsion-based synergistic dual-drug codelivery system was developed for enhanced cell apoptosis by transporting coix seed oil and etoposide into A549 (human lung carcinoma) cells simultaneously. Results obtained by dynamic light scattering showed that an etoposide (VP16)-loaded coix seed oil microemulsion (EC-ME) delivery system had a small size around 35 nm, a narrow polydispersity index, and a slightly negative surface charge. The encapsulating efficiency and total drug loading rate were 97.01% and 45.48%, respectively, by high-performance liquid chromatography. The release profiles at various pH values showed an obvious pH-responsive difference, with the accumulated amount of VP16 released at pH 4.5 (and pH 5.5) being 2.7-fold higher relative to that at pH 7.4. Morphologic alteration (particle swelling) associated with a mildly acidic pH environment was found on transmission electron microscopy. In the cell study, the EC-ME system showed a significantly greater antiproliferative effect toward A549 cells in comparison with free VP16 and the mixture of VP16 and coix seed oil. The half-maximal inhibitory concentration of the EC-ME system was 3.9-fold and 10.4-fold lower relative to that of free VP16 and a mixture of VP16 and coix seed oil, respectively. Moreover, fluorescein isothiocyanate and VP16 (the green fluorescent probe and entrapped drug, respectively) were efficiently internalized into the cells by means of coix seed oil microemulsion through intuitive observation and quantitative measurement. Importantly, an EC-ME system containing 20 μg/mL of VP16 showed a 3.3-fold and 3.5-fold improvement in induction of cell apoptosis compared with the VP-16-loaded microemulsion and free VP16, respectively. The EC-ME combination strategy holds promise as an efficient drug delivery system for induction of apoptosis and treatment of lung cancer.

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In vitro evaluation on novel modified chitosan for targeted antitumor drug delivery

Cited by 69 publications

References 41 publications

In vivopharmacokinetics, biodistribution and anti-tumor effect of paclitaxel-loaded targeted chitosan-based polymeric micelle

In vivopharmacokinetics, biodistribution and anti-tumor effect of paclitaxel-loaded targeted chitosan-based polymeric micelle

Octanoyl galactose ester-modified microemulsion system self-assembled by coix seed components to enhance tumor targeting and hepatoma therapy

Microemulsion-based synergistic dual-drug codelivery system for enhanced apoptosis of tumor cells

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