Mixed Micelles as Nano Polymer Therapeutics of Docetaxel: Increased In vitro Cytotoxicity and Decreased In vivo Toxicity

Manjappa, Arehalli S.; Kumbhar, Popat; Khopade, Prajakta S.; Patil, Ajit B.; Disouza, John

doi:10.2174/1567201814666170621113637

Cited by 13 publications

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“…Besides, we observed the peak at 1555 cm −1 corresponding to the C-O stretch of unreacted free carboxylic acid group of MTX. The peaks observed are in accordance with the previous reports [14,15]. All characteristic peaks of MTX and TPGS are present in the spectrum of MTC indicating its successful synthesis.…”

Section: Resultssupporting

confidence: 91%

“…The MTC was synthesized using the Steglich esterification reaction as per the previous report [14,15]. The MTX and TPGS were reacted at 1:1 molar ratio in DMF containing DCC and DMAP at the same molar concentration.…”

Section: Synthesis Of Mtx-tpgs Conjugate (Mtc)mentioning

confidence: 99%

“…The hemolytic ability of MTX and MTC solutions (5 and 50 μg/mL in PBS, pH 7.4) was determined using human RBCs in comparison to negative control and positive control. The hemolytic effect was determined, after 1 h incubation at 37°C, by measuring the supernatant absorbance at 420 nm [14,15].…”

Section: In Vitro Hemolysis Studymentioning

confidence: 99%

“…The 50, 000 cells/well were seeded into each well, and after overnight incubation, cells were treated with different concentrations of MTX and MTC for 24 h and 48 h in 5% CO 2 atmosphere at 37°C. The cytotoxic effect and then the IC 50 values were determined as per the previous protocol [14,15].…”

Section: In Vitro Cytotoxicitymentioning

confidence: 99%

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Ameliorated in vitro anticancer efficacy of methotrexate d-α-Tocopheryl polyethylene glycol 1000 succinate ester against breast cancer cells

et al. 2019

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Background: Methotrexate (MTX), a folate anti-metabolite, has been used widely in the treatment of plenty of malignancies. However, the clinical use is limited because of its poor water solubility (BCS class II drug), nonspecific distribution, drug resistance, short circulation half-life, and toxicity. The objective of the present research was to synthesize the ester prodrug of MTX with D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) and characterize for in vitro anticancer efficacy. Results: The FTIR and NMR results revealed the successful synthesis of the prodrug. The assay and saturation solubility of the prodrug is found to be 23 ± 2.5% and 6.7 ± 1.3 mg/mL (MTX equivalent) respectively. The CMC of the prodrug in distilled water at room temperature is found to be 36.9 ± 2.6 μg/mL. The prepared prodrug micelles showed a mean particle size of 166 ± 10 nm (PDI, 0.325 ± 0.09). Further, the TEM results confirmed the self-assembling character of the prodrug into micelles with a nearly spherical shape. The prodrug caused the significantly (p < 0.01) less hemolysis (16.8 ± 1.5%) when compared to plain MTX solution and significantly higher (p < 0.01) in vitro cytotoxicity, cell cycle arresting, and apoptosis against human breast cancer cells (MCF-7 and MDA-MB-231). Conclusion: Our study results revealed the remarkable in vitro anticancer activity of MTX following its esterification with TPGS. However, further, in vivo studies are needed to prove its efficacy against different cancers.

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Section: Resultssupporting

confidence: 91%

Section: Synthesis Of Mtx-tpgs Conjugate (Mtc)mentioning

confidence: 99%

Section: In Vitro Hemolysis Studymentioning

confidence: 99%

Section: In Vitro Cytotoxicitymentioning

confidence: 99%

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Ameliorated in vitro anticancer efficacy of methotrexate d-α-Tocopheryl polyethylene glycol 1000 succinate ester against breast cancer cells

et al. 2019

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“…Accurately weighed samples were placed in hermetically closed aluminum pans, and the empty aluminum pan was used as a reference. The samples were heated at a heating rate of 10 °C per min up to 300 °C under inert nitrogen atmosphere 13,14,15 .…”

Section: Differential Scanning Colorimetry (Dsc)mentioning

confidence: 99%

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2019

IJPSR

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The main objective of the present research was to develop mixed micelles using two biocompatible copolymers, D-α-tocopheryl polyethyleneglycol 1000 succinate (TPGS) and poloxamer 188 (P188) to improve the aqueous solubility and targeting efficacy of Simvastatin (SMV) against a variety of hormone-dependent cancers. A solvent evaporation technique prepared the plain/single copolymer micelles (SCMs) and mixed micelles (MMs). The prepared SCMs and MMs were characterized for critical micelle concentration (CMC), SMV content, particle size by dynamic light scattering (DLS), surface morphology by transmission electron microscopy (TEM), in-vitro SMV release and hemolysis. The SCMs and MMs showed mean particle size of 98 ± 5 nm and 129 ± 6 nm, respectively. SCMs showed SMV loading of 79.7 ± 5.6% while MMs exhibited improved SMV loading of 94.5 ± 6.5. The developed MMs system showed significantly lower CMC (3.5 fold less) than SCMs revealing their higher in-vivo stability. Moreover, SCMs and MMs exhibited zero order release profile, lower hemolytic behavior (<5% of hemolysis), when compared to plain SMV solution. The in-vitro cytotoxicity assay was conducted on MCF-7 (human breast cancer) cell line. Cytotoxicity studies revealed significantly improved antitumor activity of MMs when compared to SCMs and plain SMV after both incubation time points (24 and 48 h). In conclusion, the developed SMV-loaded MMs could improve the targeting and therapeutic efficacy of loaded SMV against hormone-dependent breast, prostate and ovarian carcinomas. Besides, this approach could be a potential alternative for development. However, further studies are needed to ascertain these facts. INTRODUCTION: Cancer is generally defined as an uncontrollable growth of cells due to mutations that occurs in the genes controlling the proliferation of cells. Hormone-dependent carcinomas are mainly of reproductive tract which includes prostate and testis cancer in men and breast, ovarian and endometrial cancer in women 1 .

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Supercritical fluid chromatography coupled with tandem mass spectrometry: A high‐efficiency detection technique to quantify Taxane drugs in whole‐blood samples

Jin

Guan

Dong

et al. 2017

J of Separation Science

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We present a technique to rapid determine taxane in blood samples by supercritical fluid chromatography together with mass spectrometry. The aim of this study was to develop a supercritical fluid chromatography with mass spectrometry method for the analysis of paclitaxel, cabazitaxel, and docetaxel in whole-blood samples of rats. Liquid-dry matrix spot extraction was selected in sample preparation procedure. Supercritical fluid chromatography separation of paclitaxel, cabazitaxel, docetaxel, and glyburide (internal standard) was accomplished within 3 min by using the gradient mobile phase consisted of methanol as the compensation solvent and carbon dioxide at a flow rate of 1.0 mL/min. The method was validated regarding specificity, the lower limit of quantification, repeatability, and reproducibility of quantification, extraction recovery, and matrix effects. The lower limit of quantification was found to be 10 ng/mL since it exhibited acceptable precision and accuracy at the corresponding level. All interday accuracies and precisions were within the accepted criteria of ±15% of the nominal value and within ±20% at the lower limit of quantification, implying that the method was reliable and reproducible. In conclusion, this method is a promising tool to support and improve preclinical or clinical pharmacokinetic studies with the taxanes anticancer drugs.

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Mixed Micelles as Nano Polymer Therapeutics of Docetaxel: Increased In vitro Cytotoxicity and Decreased In vivo Toxicity

Abstract: The obtained results clearly demonstrated that the developed PAADC-DP MMs system is a promising approach for cancer chemotherapy with reduced toxicity.

Cited by 13 publications

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Ameliorated in vitro anticancer efficacy of methotrexate d-α-Tocopheryl polyethylene glycol 1000 succinate ester against breast cancer cells

Ameliorated in vitro anticancer efficacy of methotrexate d-α-Tocopheryl polyethylene glycol 1000 succinate ester against breast cancer cells

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Supercritical fluid chromatography coupled with tandem mass spectrometry: A high‐efficiency detection technique to quantify Taxane drugs in whole‐blood samples

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