Folate-Modified Cholesterol-Bearing Pullulan, a New Cancer-Targeted                 Nanoparticle Drug Carrier: Synthesis and Applications

Sunamoto, Junzo; Ushio, Kazutoshi; Lai, Douglas T.

doi:10.1177/0883911506071967

Cited by 9 publications

(7 citation statements)

References 13 publications

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“…The FA-CHP used in this study was prepared as reported previously [15], with slight modifications. The chemical structure of FA-CHP is shown in Figure 1.…”

Section: Resultsmentioning

confidence: 99%

“…FA-CHP used in this study was prepared as reported previously [15] with slight modifications. Briefly, CHP (8 g) was activated by 4-nitrophenyl chloroformate (PNPC), before conjugating with folic acid ␥-2-aminorthylamide (EDA-FA).…”

Section: Synthesis Of Fa-chpmentioning

confidence: 99%

“…Subsequently, we synthesized a FA-CHP [15]. The purpose of this study was to clarify whether FA-CHP complexed with an anticancer drug exhibits selective cytotoxicity via FR against cancer cells in vitro and in vivo.…”

Section: Introductionmentioning

confidence: 99%

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Selective and Effective Cytotoxicity of Folic Acidconjugated Cholesteryl Pullulan Hydrogel Nanoparticles Complexed with Doxorubicin inΓIn Vitro and ΓIn Vivo Studies

Hidaka

Kanematsu

Ushio

et al. 2006

Journal of Bioactive and Compatible Polymers

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We previously reported that cholesteryl pullulan (CHP) derivatives were effective carriers drug delivery systems in targeting cancer cells. We have now synthesized folic acid-conjugated CHP hydrogel nanoparticles (FACHP). FA-CHP complexed with the anticancer drug doxorubicin (DOX) show a higher cytotoxicity than CHP complexed with DOX in in vitro studies. The expression of a folate receptor (FR) is elevated in many cancers; in this case, confocal image analysis revealed that FA-CHP complexed with DOX exhibited greater cellular uptake than CHP complexed with DOX in human epidermal carcinoma (KB) cells over-expressing surface FR. In vivo studies showed that the increase of tumor volume in a nude mice xenograft model was significantly suppressed. Accordingly, FA-CHP may be an effective vehicle for the delivery of anticancer drugs and has a potential application in the treatment of overexpressing FR solid tumor cells.

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“…The FA-CHP used in this study was prepared as reported previously [15], with slight modifications. The chemical structure of FA-CHP is shown in Figure 1.…”

Section: Resultsmentioning

confidence: 99%

Section: Synthesis Of Fa-chpmentioning

confidence: 99%

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Selective and Effective Cytotoxicity of Folic Acidconjugated Cholesteryl Pullulan Hydrogel Nanoparticles Complexed with Doxorubicin inΓIn Vitro and ΓIn Vivo Studies

Hidaka

Kanematsu

Ushio

et al. 2006

Journal of Bioactive and Compatible Polymers

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“…Pullulan targets the liver and has anticancer activity (Hosseinkhani et al, 2002;Sunamoto et al, 2006). SAP nanoparticles were tested without ATRA on hepatocellular carcinoma HepG2 cells using the MTT assay.…”

Section: In Vitro Drug Release and Cytotoxicity On Cancer Cellsmentioning

confidence: 99%

Preparation and characterization of stearic acid-pullulan nanoparticles

Kim

2010

Arch. Pharm. Res.

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For a new anticancer drug carrier, we synthesized 4 compositions of amphiphilic stearic acidconjugated pullulan (SAP) and characterized them with FT-IR spectroscopy. Crystalline changes were verified by x-ray diffraction patterns before and after synthesis of the SAP conjugate. SAP nanoparticles were prepared by a diafiltration method, and the fluorescence spectroscopy using pyrene showed particle self-assembly in water. SAP nanoparticles were spherical in TEM photos, and particle size ranged between 200 approximately 500 nm in photon correlation spectroscopy. Release of all-trans-retinoic acid from the SAP nanoparticles was maintained over 5 weeks. For further study in vivo, we tested the cytotoxicity of SAP nanoparticles using an MTT assay, and cytotoxicity was augmented as the molar mass of stearic acid increased in human liver carcinoma HepG2 cells. Therefore, SAP nanoparticles might be a promising longterm delivery carrier for hydrophobic therapeutic molecules with the appropriate composition.

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“…Many investigations have reported that some amphiphilic pullulan derivatives can form self-aggregated NPs to be used as the carrier for drug delivery (Zhang et al, 2009;Yang et al, 2010;Lee et al, 2012;Yang et al, 2014). Cholesterol-modified pullulan (CHP), as one of amphiphilic pullulan derivatives, can be synthesized using 1,6-hexyldiisocyanate linkages by the reaction between cholesterol and pullulan (Akiyoshi et al, 1993), and its selfaggregated CHP NPs can be used as drug delivery systems (Akiyoshi et al, 1998;Ikuta et al, 2002;Sunamoto et al, 2006;Shimoda et al, 2012) or artificial molecular chaperones (Nomura et al, 2003;Asayama et al, 2008). The outstanding characteristics of cholesterol-modified pullulan attract our group to engage in this research.…”

Section: Introductionmentioning

confidence: 99%

The preliminary evaluation on cholesterol-modified pullulan as a drug nanocarrier

Shen

Yang

2014

Drug Delivery

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To further develop cholesterol-modified pullulan self-aggregated nanoparticles (CHSPNs) as a drug nanocarrier, CHSP was synthesized and characterized. Its cholesterol degree determined by 1 H NMR was 5.2 cholesterol groups per hundred glucose units. CHSPNs were prepared in aqueous media and characterized by dynamic laser light-scattering (DLS), zeta potential and transmission electron microscopy (TEM). These nanoparticles were almost spherical in shape, and the zeta potentials of CHSPNs were near zero in aqueous media. CHSPNs can be stable at least 2 months with no significant size and zeta potential changes. Single dose toxicity test in mice was investigated for the safety evaluation of CHSPNs as a drug nanocarrier, and the result showed CHSPNs were well tolerated at the dose of 200 mg/kg in mice. Epirubicin (EPI)-loaded CHSPNs (EPI-CHSPNs) were prepared and the in vivo pharmacokinetics and biodistribution were studied. Compared with the EPI solution, EPI-CHSPNs have exhibited higher plasma drug concentration, longer half-life time (t 1/2 ) and the larger area under-the-curve (AUC). Moreover, the drug level of EPI-CHSPNs increased in liver and decreased in heart. The results indicated that CHSPNs were stable, safe and may be a promising drug delivery carrier.

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Folate-Modified Cholesterol-Bearing Pullulan, a New Cancer-Targeted Nanoparticle Drug Carrier: Synthesis and Applications

Cited by 9 publications

References 13 publications

Selective and Effective Cytotoxicity of Folic Acidconjugated Cholesteryl Pullulan Hydrogel Nanoparticles Complexed with Doxorubicin inΓIn Vitro and ΓIn Vivo Studies

Selective and Effective Cytotoxicity of Folic Acidconjugated Cholesteryl Pullulan Hydrogel Nanoparticles Complexed with Doxorubicin inΓIn Vitro and ΓIn Vivo Studies

Preparation and characterization of stearic acid-pullulan nanoparticles

The preliminary evaluation on cholesterol-modified pullulan as a drug nanocarrier

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