Hydrotropic Polymeric Mixed Micelles Based on Functional Hyperbranched Polyglycerol Copolymers as Hepatoma-Targeting Drug Delivery System

Zhang, Xuejiao; Zhang, Xinge; Yu, Peien; Han, Yucai; Li, Yangguang; Li, Chaoxing

doi:10.1002/jps.23344

Cited by 24 publications

(9 citation statements)

References 37 publications

(36 reference statements)

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“…Over the past few years, application of targeted drug delivery systems have been of considerable interest in disease management, especially active targeting. [4][5][6] Researchers have shown that surface functionalization of nanomaterials using glycyrrhetinic acid (GA) as a drug delivery targeting ligand was beneficial to the defined receptor recognition on the surface of hepatoma cells. [7][8][9] Generally, nanotechnology with preferred surface functionalization has the potential to improve the treatment of liver cancer.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, characterization, and in vitro evaluation of curcumin-loaded albumin nanoparticles surface-functionalized with glycyrrhetinic acid

Li¹,

Chen²,

Deng³

et al. 2015

IJN

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We have designed and developed curcumin (Ccn)-loaded albumin nanoparticles (BNPs) surface-functionalized with glycyrrhetinic acid (Ccn-BNP-GA) for GA receptor-mediated targeting. Ccn-BNP-GA was prepared by conjugating GA as a hepatoma cell-specific binding molecule onto the surface of BNPs. Ccn-BNP-GA showed a narrow distribution with an average size of 258.8±6.4 nm, a regularly spherical shape, an entrapment efficiency of 88.55%±5.54%, and drug loading of 25.30%±1.58%. The density of GA as the ligand conjugated to BNPs was 140.48±2.784 μg/g bovine serum albumin. Cytotoxicity assay results indicated that Ccn-BNP-GA was significantly more cytotoxic to HepG2 cells and in a concentration-dependent manner. Ccn-BNP-GA also appeared to be taken up to a greater extent by HepG2 cells than undecorated groups, which might be due to the high affinity of GA for GA receptors on the HepG2 cell surface. These cytotoxicity assay results were corroborated by analysis of cell apoptosis and the cell cycle. Further, Ccn-BNP-GA showed an approximately twofold higher rate of cell apoptosis than the other groups. Moreover, proliferation of HepG2 cells was arrested in G 2 /M phase based on cell cycle analysis. These results, which were supported by the GA receptor-mediated endocytosis mechanism, indicate that BNPs surface-functionalized with GA could be used in targeted cancer treatment with high efficacy, sufficient targeting, and reduced toxicity.

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Section: Introductionmentioning

confidence: 99%

Synthesis, characterization, and in vitro evaluation of curcumin-loaded albumin nanoparticles surface-functionalized with glycyrrhetinic acid

Li¹,

Chen²,

Deng³

et al. 2015

IJN

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“…27 The plasma cardiac output (Q co ) for rats was calculated as 2.69 L/hour. The mass balance equations (1)(2)(3)(4)(5)(6)(7)(8) for the model are shown as follows: …”

Section: Pbpk Modeling and Fittingmentioning

confidence: 99%

“…6 Of these, micelles are becoming a powerful tool for systemic delivery of insoluble drugs. [7][8][9][10][11] Micelles are colloidal nanoparticulates self-assembled from amphiphilic molecules with a hydrophobic core inside and a hydrophilic shell outside.…”

Section: Introductionmentioning

confidence: 99%

Mixed nanomicelles as potential carriers for systemic delivery of Z-GP-Dox, an FAPα-based doxorubicin prodrug: formulation and pharmacokinetic evaluation

Zhang¹,

Zhang²,

Li³

et al. 2015

IJN

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Z-GP-Dox, the FAPα (fibroblast activation protein-α)-based doxorubicin prodrug, demonstrates excellent tumor targeting effects and a favorable toxicokinetic profile. However, the insoluble nature of Z-GP-Dox becomes a significant barrier to drug administration, particularly when it comes to the clinical stage. Here we developed a nanomicelle system to facilitate the systemic delivery of Z-GP-Dox, and evaluated its disposition in rats following administration of the micelles using a physiologically-based pharmacokinetic model. Z-GP-Dox-loaded mixed nanomicelles (ZGD-MNs) were prepared by dispersion of an ethanol solution of Z-GP-Dox, lecithin, and sodium oleate in water. The obtained ZGD-MNs were 86.6 nm in size with a drug loading of 14.03%. ZGD-MNs were fairly stable in phosphate-buffered saline and showed satisfactory physical and chemical stability over a 2-week observation period. Accumulative drug release was more than 56% within 24 hours. Further, the physiologically-based pharmacokinetic rat model consisting of various organs (ie, heart, liver, spleen, lung, kidney, and intestine) was fitted to the experimental data following administration of ZGD-loaded cosolvent (control) or micelles. Derived partition coefficient values revealed that the nanomicelles significantly altered the biodistribution of Z-GP-Dox. Of note, drug distribution to the lung, liver, and spleen was greatly enhanced and the fold change ranged from 2.4 to 33. In conclusion, this is the first report of a mixed micelle system being a viable carrier for delivery of Z-GP-Dox. Also, the pharmacokinetic behavior of Z-GP-Dox was satisfactorily described by the physiologically-based pharmacokinetic model.

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“…Nano-drug systems are well-established approaches to meeting the formulation challenges of insoluble drugs. 2 These promising carriers include liposomes, 3,4 micro-/nanoemulsions, 5 micelles, 6,7 solid lipid nanoparticles, 8 polymeric nanoparticles, 9 and nanocrystals. 10 Of these, liposomes and lipid emulsions have been successfully developed into injectable products such as Doxil ® and Diprivan ® .…”

Section: Introductionmentioning

confidence: 99%

Elucidating the in vivo fate of nanocrystals using a physiologically based pharmacokinetic model: a case study with the anticancer agent SNX-2112

Dong

Wang

et al. 2015

IJN

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Introduction SNX-2112 is a promising anticancer agent but has poor solubility in both water and oil. In the study reported here, we aimed to develop a nanocrystal formulation for SNX-2112 and to determine the pharmacokinetic behaviors of the prepared nanocrystals. Methods Nanocrystals of SNX-2112 were prepared using the wet-media milling technique and characterized by particle size, differential scanning calorimetry, drug release, etc. Physiologically based pharmacokinetic (PBPK) modeling was undertaken to evaluate the drug’s disposition in rats following administration of drug cosolvent or nanocrystals. Results The optimized SNX-2112 nanocrystals (with poloxamer 188 as the stabilizer) were 203 nm in size with a zeta potential of −11.6 mV. In addition, the nanocrystals showed a comparable release profile to the control (drug cosolvent). Further, the rat PBPK model incorporating the parameters of particulate uptake (into the liver and spleen) and of in vivo drug release was well fitted to the experimental data following administration of the drug nanocrystals. The results reveal that the nanocrystals rapidly released drug molecules in vivo, accounting for their cosolvent-like pharmacokinetic behaviors. Due to particulate uptake, drug accumulation in the liver and spleen was significant at the initial time points (within 1 hour). Conclusion The nanocrystals should be a good choice for the systemic delivery of the poorly soluble drug SNX-2112. Also, our study contributes to an improved understanding of the in vivo fate of nanocrystals.

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Hydrotropic Polymeric Mixed Micelles Based on Functional Hyperbranched Polyglycerol Copolymers as Hepatoma-Targeting Drug Delivery System

Cited by 24 publications

References 37 publications

Synthesis, characterization, and in vitro evaluation of curcumin-loaded albumin nanoparticles surface-functionalized with glycyrrhetinic acid

Synthesis, characterization, and in vitro evaluation of curcumin-loaded albumin nanoparticles surface-functionalized with glycyrrhetinic acid

Mixed nanomicelles as potential carriers for systemic delivery of Z-GP-Dox, an FAPα-based doxorubicin prodrug: formulation and pharmacokinetic evaluation

Elucidating the in vivo fate of nanocrystals using a physiologically based pharmacokinetic model: a case study with the anticancer agent SNX-2112

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Hydrotropic Polymeric Mixed Micelles Based on Functional Hyperbranched Polyglycerol Copolymers as Hepatoma-Targeting Drug Delivery System

Cited by 24 publications

References 37 publications

Synthesis, characterization, and in vitro evaluation of curcumin-loaded albumin nanoparticles surface-functionalized with glycyrrhetinic acid

Synthesis, characterization, and in vitro evaluation of curcumin-loaded albumin nanoparticles surface-functionalized with glycyrrhetinic acid

Mixed nanomicelles as potential carriers for&nbsp;systemic delivery of Z-GP-Dox, an FAP&alpha;-based doxorubicin prodrug: formulation and pharmacokinetic evaluation

Elucidating the in vivo fate of nanocrystals using a physiologically based pharmacokinetic model: a&nbsp;case study with the anticancer agent SNX-2112

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Product

Resources

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Mixed nanomicelles as potential carriers for systemic delivery of Z-GP-Dox, an FAPα-based doxorubicin prodrug: formulation and pharmacokinetic evaluation

Elucidating the in vivo fate of nanocrystals using a physiologically based pharmacokinetic model: a case study with the anticancer agent SNX-2112