Development of PLGA Nanoparticles Simultaneously Loaded with Vincristine and Verapamil for Treatment of Hepatocellular Carcinoma

Song, Xiang Rong; Zheng, Yu; He, Gu; Yang, Li; Luo, You; He, Zhi Yao; Li, Shuang Zhi; Li, Jun Ming; Yu, Shui; Luo, Xun; Hou, Shi; Wei, Yu Quan

doi:10.1002/jps.22200

Cited by 69 publications

(36 citation statements)

References 20 publications

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“…51 The size from TEM image seemed much smaller than that obtained by the Zetasizer Nano ZS90, possibly attributing to the shrinkage of micelles shell during the process of drying. 52 Morphology captured by AFM showed that a few micelles had nonspherical shape and bigger size than that observed in TEM image, probably owing to minor aggregation of micelles. Additionally, the zeta potential of QC-loaded micelles (−22 mv) was close to that of blank micelles.…”

Section: Characterization Of Qc-loaded Micellesmentioning

confidence: 89%

Micelles Based on Methoxy Poly(Ethylene Glycol)Cholesterol Conjugate for Controlled and Targeted Drug Delivery of a Poorly Water Soluble Drug

He²,

Yu³

et al. 2012

Journal of Biomedical Nanotechnology

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In this study, quercetin (QC) with cancer chemoprevention effect and anticancer potential was loaded into polymeric micelles of methoxy poly(ethylene glycol)-cholesterol conjugate (mPEG-Chol) in order to increase its water solubility. MPEG-Chol with lower critical micelle concentration (CMC) value (4 0 × 10 −7 M ∼ 13 × 10 −7 M) was firstly synthesized involving two steps of chemical modification on cholesterol by esterification, and then QC was incorporated into mPEG-Chol micelles by self-assembly method. After the process parameters were optimized, QC-loaded micelles had higher drug loading (3.66%) and entrapment efficiency (93.51%) and nano-sized diameter (116 nm). DSC analysis demonstrated that QC had been incorporated non-covalently into the micelles and existed as an amorphous state or a solid solution in the polymeric matrix. The freeze-dried formulation with addition of 1% (w/v) mannitol as cryoprotectant was successfully developed for the long-term storage of QC-loaded micelles. Compared to free QC, QC-loaded micelles could release QC more slowly. Moreover, the release of QC from micelles was slightly faster in PBS at pH 5 than that in PBS at pH 7.4, which implied that QC-loaded micelles might be pH-sensitive and thereby selectively deliver QC to tumor tissue with unwanted side effects. Therefore, mPEG-Chol was a promising micellar vector for the controlled and targeted drug delivery of QC to tumor and QCloaded micelles were also worth being further investigated as a potential formulation for cancer chemoprevention and treatment.

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Section: Characterization Of Qc-loaded Micellesmentioning

confidence: 89%

Micelles Based on Methoxy Poly(Ethylene Glycol)Cholesterol Conjugate for Controlled and Targeted Drug Delivery of a Poorly Water Soluble Drug

He²,

Yu³

et al. 2012

Journal of Biomedical Nanotechnology

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“…PLP and F-PLP cytotoxicity was evaluated in the CT26 cell line by MTT assay as previously described [48]. Briefly, cells were seeded on 96-well plates (Corning Inc., NY, US) at a density of 3,000 cells/ well with 100 μL RPMI-1640.…”

Section: Methodsmentioning

confidence: 99%

A folate receptor-targeted lipoplex delivering interleukin-15 gene for colon cancer immunotherapy

et al. 2016

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Interleukin-15 has been implicated as a promising cytokine for cancer immunotherapy, while folate receptor α (FRα) has been shown to be a potentially useful target for colon cancer therapy. Herein, we developed F-PLP/pIL15, a FRα-targeted lipoplex loading recombinant interleukin-15 plasmid (pIL15) and studied its antitumor effects in vivo using a CT26 colon cancer mouse model. Compared with control (normal saline) treatment, F-PLP/pIL15 significantly suppressed tumor growth in regard to tumor weight (P < 0.001) and reduced tumor nodule formation (P < 0.001). Moreover, when compared to other lipoplex-treated mice, F-PLP/pIL15-treated mice showed higher levels of IL15 secreted in the serum (P < 0.001) and ascites (P < 0.01). These results suggested that the targeted delivery of IL15 gene might be associated with its in vivo antitumor effects, which include inducing tumor cell apoptosis, inhibiting tumor proliferation and promoting the activation of immune cells such as T cells and natural killer cells. Furthermore, hematoxylin and eosin staining of vital organs following F-PLP/pIL15 treatment showed no detectable toxicity, thus indicating that intraperitoneal administration may be a viable route of delivery. Overall, these results suggest that F-PLP/pIL15 may serve as a potential targeting preparation for colon cancer therapy.

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“…Cytotoxicity of FLP/PEDF was carried out by MTT assay on HeLa cells and HUVEC cells as described previously27. In brief, cells were planted into 96-well plates (Corning Inc., NY, USA) at a density of 3 × 10 3 cells per well in 100 μL medium.…”

Section: Methodsmentioning

confidence: 99%

Promising Nanocarriers for PEDF Gene Targeting Delivery to Cervical Cancer Cells Mediated by the Over-expressing FRα

Yang

Liu

et al. 2016

Sci Rep

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Cervical cancer presents extremely low PEDF expression which is associated with tumor progression and poor prognosis. In this study, folate receptor α (FRα)-targeted nano-liposomes (FLP) were designed to enhance the anti-tumor effect by targeting delivery of exogenous PEDF gene to cervical cancer cells. The targeting molecule F-PEG-Chol was firstly synthesized by a novel simpler method. FLP encapsulating PEDF gene (FLP/PEDF) with a typical lipid-membrane structure were prepared by a film dispersion method. The transfection experiment found FLP could effectively transfect human cervical cancer cells (HeLa cells). FLP/PEDF significantly inhibited the growth of HeLa cells and human umbilical vein endothelial cells (HUVEC cells) and suppressed adhension, invasion and migration of HeLa cells in vitro. In the abdominal metastatic tumor model of cervical cancer, FLP/PEDF administered by intraperitoneal injection exhibited a superior anti-tumor effect probably due to the up-regulated PEDF. FLP/PEDF could not only sharply reduce the microvessel density but also dramatically inhibit proliferation and markedly induce apoptosis of tumor cells in vivo. Moreover, the preliminary safety investigation revealed that FLP/PEDF had no obvious toxicity. These results clearly showed that FLP were desired carriers for PEDF gene and FLP/PEDF might represent a potential novel strategy for gene therapy of cervical cancer.

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Development of PLGA Nanoparticles Simultaneously Loaded with Vincristine and Verapamil for Treatment of Hepatocellular Carcinoma

Cited by 69 publications

References 20 publications

Micelles Based on Methoxy Poly(Ethylene Glycol)Cholesterol Conjugate for Controlled and Targeted Drug Delivery of a Poorly Water Soluble Drug

Micelles Based on Methoxy Poly(Ethylene Glycol)Cholesterol Conjugate for Controlled and Targeted Drug Delivery of a Poorly Water Soluble Drug

A folate receptor-targeted lipoplex delivering interleukin-15 gene for colon cancer immunotherapy

Promising Nanocarriers for PEDF Gene Targeting Delivery to Cervical Cancer Cells Mediated by the Over-expressing FRα

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