Long-circulating poly(ethylene glycol)-coated emulsions to target solid tumors

Rossi, John; Giasson, Suzanne; Khalid, Mohamed Nabil; Delmas, Pascal; Allen, Christine; Leroux, Jean‐Christophe

doi:10.1016/j.ejpb.2007.03.016

Cited by 35 publications

(31 citation statements)

References 43 publications

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“…Meanwhile, considerable emphasis has been given to develop emulsion systems as drug carrier system because of its improved solubilization for water-insoluble and/or oil insoluble active compounds, modified drug release characteristic, protecting drug from transformation and delivering drugs into some tissues specifically after intravenous administration (12)(13)(14)(15)(16). Being a class of stable emulsions composed of discrete oil phase and continuous aqueous phase separated by a monolayer of surfactants with particle diameter usually less than 100 nm (17), nanoemulsion have been shown to increase bioavailability and efficacy of a number of compounds such as insulin and paclitaxel (18,19).…”

Section: Introductionmentioning

confidence: 99%

A Novel Camptothecin Derivative Incorporated in Nano-Carrier Induced Distinguished Improvement in Solubility, Stability and Anti-tumor Activity Both In Vitro and In Vivo

Han

Fang

et al. 2008

Pharm Res

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Purpose. An oil/water nanoemulsion was developed in the present study to enhance the solubility, stability and anti-tumor activity of a novel 10-methoxy-9-nitrocamptothecin (MONCPT). Materials and Methods. MONCPT nanoemulsion was prepared using Lipoid E80 and cremophor EL as main emulsifiers by microfluidization. The droplet size of the nanoemulsion was measured by dynamic light scattering. In vitro drug release was monitored by membrane dialysis. Kinetics of MONCPT transformed into carboxylic salt was performed in phosphate buffer at different pH. Hemolysis of MONCPT nanoemulsion was conducted in rabbit erythrocytes. Solubilization character of MONCPT in nanoemulsion was experimented using Nile red as a solvatochromic probe. In vitro cytotoxicity of the nanoemulsion was measured in A549 and S180 cells using Sulforhodamine B protein stain method, and suppression rate of tumor growth was investigated in S180-bearing mice. The cell cycle effects of MONCPT nanoemulsion on S180 cells were analyzed by flow cytometry. Distribution of the nanoemulsion in A549 cells and S180-bearing mice were also investigated by fluorescence image. Results. MONCPT is incorporated in the nanoemulsion in form of lactone with concentration of 489 µg/ml, more than 200 folds higher than that in water. Experiments using Nile red as a solvatochromic probe indicated that more MONCPT might be located in the interfacial surfactant layer of the nanoemulsion than that in discrete oil droplet or continuous aqueous phase. Nanoemulsion could release MONCPT in a sustained way, and it was further shown to notably postpone the hydrolysis of MONCPT with longer hydrolysis half-life time (11.38 h) in nanoemulsion at pH 7.4 than that of MONCPT solution (4.03 h). No obvious hemolysis was caused by MOCPT nanoemulsion in rabbit erythrocytes. MONCPT nanoemulsion showed a marked increase in cytotoxic activity, 23.6 folds and 28.6 folds in S180 cells and A549 cells respectively via arresting the cell at G2 phase, compared to that induced by MONCPT injection. It correlated well to the in vivo anti-tumor activity of MONCPT nanoemulsion with suppression rate of 93.6%, while that of MONCPT injection was only 24.2% at the same dosage. Moreover, nanoemulsion exhibited enhanced capability of delivering drug into malignant cell's nucleus in vitro and induced drug accumulation in tumor in S180-bearing mice using in vivo imaging. Conclusion. The nanoemulsion prepared exhibited an improved MONCPT solubility, stability and antitumor activity, providing a promising carrier for cancer chemotherapy using MONCPT.

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Section: Introductionmentioning

confidence: 99%

A Novel Camptothecin Derivative Incorporated in Nano-Carrier Induced Distinguished Improvement in Solubility, Stability and Anti-tumor Activity Both In Vitro and In Vivo

Han

Fang

et al. 2008

Pharm Res

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“…Various nanoparticulate PTX formulations such as lipid nanoparticles, 4) polymeric micelles, 5-8) liposomes 9-13) and emulsions [14][15][16][17][18][19] have been examined, and all of these formulations achieved certain improvements in PTX solubility. Besides them, Abraxane ® in which PTX is formulated within albumin particles is also known to successfully improve PTX solubility.…”

Section: 3)mentioning

confidence: 99%

“…2,3) Since these problems associated with the current PTX formulation are mainly ascribed to the poor aqueous solubility and non-specific in vivo disposition characteristics of PTX, a lot of attention has been paid to developing a safer PTX dosage form with higher PTX solubilizing capability and better tumor targeting properties while reducing non-specific disposition to other tissues/organs. Various nanoparticulate PTX formulations such as lipid nanoparticles, 4) polymeric micelles, [5][6][7][8] liposomes [9][10][11][12][13] and emulsions [14][15][16][17][18][19] have been examined, and all of these formulations achieved certain improvements in PTX solubility. Besides them, Abraxane ® in which PTX is formulated within albumin particles is also known to successfully improve PTX solubility.…”

mentioning

confidence: 99%

Formulation and Evaluation of Paclitaxel-Loaded Polymeric Nanoparticles Composed of Polyethylene Glycol and Polylactic Acid Block Copolymer

Araki

Kono

Ogawara

et al. 2012

Biological & Pharmaceutical Bulletin

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To develop potent paclitaxel (PTX) formulations for cancer chemotherapy, we formulated PTX into polymeric nanoparticles composed of polyethylene glycol (PEG) and polylactic acid (PLA) block copolymer (PN-PTX). First, the physicochemical properties of PN-PTX prepared were assessed; the mean particle size was around 80 nm and the zeta potential was found to be almost neutral. Next, the in vitro PTX release property was assessed by a dialysis method. Although rapid release of PTX was observed just after dosing, around 70% of PTX was stably incorporated in polymeric nanoparticles for a long time in the presence of serum. Then, the in vivo pharmacokinetics of PN-PTX after intravenous administration was investigated in Colon-26 (C26) tumor-bearing mice. Both polymeric nanoparticles and PTX incorporated exhibited a long blood circulating property, leading to enhanced permeability and retention (EPR) effect-driven, time-dependent tumor disposition of PTX. Tumor distribution increased gradually for 24 h, and tissue uptake clearance of polymeric nanoparticles in the liver and spleen was lower than that of PEG liposomes. Since these results indicated that the in vivo disposition characteristics of PN-PTX were very favorable, we then evaluated the anti-tumor effect of PN-PTX in C26 tumor-bearing mice. However, PN-PTX did not exhibit any significant anti-tumor effect, presumably due to the poor PTX release from polymeric nanoparticles. From these results, it is considered that the favorable pharmacokinetic properties of nanoparticles and the drug incorporated do not always lead to its potent in vivo pharmacological activity, suggesting the importance of PTX release properties within tumor tissues.Key words paclitaxel; block-copolymer; nanoparticle; enhanced permeability and retention effect Paclitaxel (PTX) belongs to the taxane family of anti-cancer agents, and has been demonstrated to exert good clinical anticancer efficacy in various cancers including ovarian, breast, head and neck, and non-small cell lung cancers.1) Due to its poor aqueous solubility, the commercially available product for intravenous infusion of PTX, known as Taxol ® , formulates PTX in a 1 : 1 mixture of Cremophor EL (polyethoxylated castor oil) and ethanol. However, Cremophor EL has been considered to be associated with severe adverse effects such as hypersensitivity, neurotoxicity, and nephropathia. Premedication with corticosteroids and antihistamines is therefore used to reduce the intensity and incidence of these side effects. 2,3)Since these problems associated with the current PTX formulation are mainly ascribed to the poor aqueous solubility and non-specific in vivo disposition characteristics of PTX, a lot of attention has been paid to developing a safer PTX dosage form with higher PTX solubilizing capability and better tumor targeting properties while reducing non-specific disposition to other tissues/organs. Various nanoparticulate PTX formulations such as lipid nanoparticles, 4) polymeric micelles, 5-8) liposomes 9-13) and emulsions [14][15...

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“…Because LEs are expected to act as good drug carriers because of their high lipophilicity and apolarity, which allows them to cross cell membranes, they have also been used as parenteral DDS carriers [6] for sites of inflammation [7], as well as the heart [8] and lymphatic system [9], because of their tendency to accumulate in these areas. Moreover, recently, LEs have been employed as carriers of anticancer agents to improve their therapeutic indices and minimize drug cytotoxicity in normal cells [10][11][12][13][14][15][16]. It has been recognized that only drug carriers less than 100 nm in diameter can pass through the discontinuous capillary endothelium of tumors [17].…”

Section: Introductionmentioning

confidence: 99%

Application of 19F NMR Spectroscopy Using a Novel a-Tocopherol Derivative as a 19F NMR Probe for a Pharmacokinetic Study of Lipid Nano-Emulsions in Mice

H¹

2015

Pharm Anal Acta

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Long-circulating poly(ethylene glycol)-coated emulsions to target solid tumors

Cited by 35 publications

References 43 publications

A Novel Camptothecin Derivative Incorporated in Nano-Carrier Induced Distinguished Improvement in Solubility, Stability and Anti-tumor Activity Both In Vitro and In Vivo

A Novel Camptothecin Derivative Incorporated in Nano-Carrier Induced Distinguished Improvement in Solubility, Stability and Anti-tumor Activity Both In Vitro and In Vivo

Formulation and Evaluation of Paclitaxel-Loaded Polymeric Nanoparticles Composed of Polyethylene Glycol and Polylactic Acid Block Copolymer

Application of 19F NMR Spectroscopy Using a Novel a-Tocopherol Derivative as a 19F NMR Probe for a Pharmacokinetic Study of Lipid Nano-Emulsions in Mice

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