Development and validation of a stability indicating isocratic HPLC method for gemcitabine with application to drug release from poly lactic-co-glycolic acid nanoparticles and enzymatic degradation studies

Chen, Guan-Yu; Svirskis, Darren; Wen, Jingyuan

doi:10.1111/jphp.12470

Cited by 15 publications

(11 citation statements)

References 27 publications

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“…The difference in the effective number of polymers evaluated was likely the reason for the higher shear stress observed in this experiment. Upon the addition of NaOH solution to adjust pH to 7.4, carboxyl groups on the carbomers (pKa 3-5) are ionized, leading to electrostatic repulsion and dramatically increasing the rigidity of the formulation structure [23]. Thus, the ionized carboxylic groups could have also interacted with the small but very positive sodium ions, leading to a reduction in viscosity and shear stress.…”

Section: Discussionmentioning

confidence: 99%

Formulation and Characterization of Glutathione-Loaded Bioadhesive Hydrogel for Ocular Delivery

Wen¹

2019

AJOP

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Glutathione may prevent age-related, oxidative damage to ocular tissues but has poor corneal penetration. Hydrogel formulations were investigated to determine an optimized ocular delivery system. The rheology and texture profile of formulations were investigated at 25°C. The 1% w/v glutathione was incorporated into systems demonstrating desirable characteristics for ocular vehicles and physical characteristics re-determined. In vitro cumulative glutathione delivery across the bovine cornea was measured over 8 hours at 32ºC in Franz diffusion cells. Carbopol-containing Poloxamer systems exhibited shear-thinning behavior desirable for ocular formulations whilst Polyvinyl alcohol (PVA) and Polyacrylic acid (PAA) systems exhibited Newtonian behavior. Of the glutathione-containing systems, 0.2% w/v Carbopol 1342 was the most viscous with a viscosity of 960cP at a shear rate of 100sec-1. All formulations significantly increased the amount of glutathione delivered across the cornea (relative to an aqueous solution of glutathione) with the exception of 0.1% w/v Carbopol 940 (p=0.12). Formulations containing 0.1% w/v Carbopol 934, 0.1% w/v Carbopol 1342 and 0.2% w/v Carbopol 940 improved penetration dramatically (ca. 30%); but were not significantly different from each other. Therefore, Carbopol and Poloxamer formulations demonstrated enhanced penetration of glutathione across the cornea. The 0.2% w/v C940-containing-Poloxamer formulation was determined to be the most promising for ocular delivery of glutathione.

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Section: Discussionmentioning

confidence: 99%

Formulation and Characterization of Glutathione-Loaded Bioadhesive Hydrogel for Ocular Delivery

Wen¹

2019

AJOP

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“…An aliquot sample of 0.5 mL was withdrawn at different time intervals over 12 hours, and replaced by 0.5 mL of fresh medium. All the samples were filtered by 0.22 µm MS® PES syringe filters prior to HPLC determination 13 . All experiments were conducted with triplicates, and results are given as mean ± SD.…”

Section: In-vitro Drug Release Studiesmentioning

confidence: 99%

Untitled

2018

IJPSR

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The sublingual delivery of drugs represents a continuing challenge, as well as an opportunity. In this study, a poly (lactic-co-glycolic acid) (PLGA) based Water-in-Oil-in-Water (w/o/w) double emulsion of nanoparticles was developed as potential platform technology, to generate sustained drug release profile and maximize the bioavailability of the glutathione (GSH). Two-level full factorial design was carried out based on different types and concentrations of the stabilizers used, and on varying sonication time. The optimal formulations were predicted with particle size of 232.57 ± 20.56 nm, zeta-potential of -12.33 ± 0.20 mV and entrapment efficiency of 77.04 ± 1.50%. Spherical particle morphology and uniform size was observed by scanning electron microscopy. Sustained release profile was achieved and the release kinetics was illustrated as a Korsmeyer -Peppas kinetic model. Moreover, in ex-vivo permeation studies, approximately 2-fold increase in the transmucosal permeation of GSH was achieved when PVA and carbopol were incorporated with the nanoparticulate delivery system, resulting in 21.9 ± 1.2% drug permeation and a permeation coefficient of (4.96 ± 0.36) × 10 -6 cm•sec -1 . The developed PLGA nanoparticulate delivery system was able to elevate the retention time and resist saliva dissolution, providing a sustained drug release profile and relatively high transmucosal permeation of GSH.

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“…Gemcitabine ([GEM]; 2′,2′‐difluorodeoxycytidine [dFdC]) is commonly used in chemotherapy for ovarian cancer, non–small‐cell lung cancer, breast cancer, and pancreatic cancer . GEM is a prodrug, after entering the cells, it can be phosphorylated stepwise by deoxycytidine kinase (dCK) into active 2′,2′‐difluorodeoxycytidine triphosphate (dFdCTP) metabolite .…”

Section: Introductionmentioning

confidence: 99%

“…Gemcitabine ([GEM]; 2′,2′-difluorodeoxycytidine [dFdC]) is commonly used in chemotherapy for ovarian cancer, non-small-cell lung cancer, breast cancer, and pancreatic cancer. [3][4][5] GEM is a prodrug, after entering the cells, it can be phosphorylated stepwise by deoxycytidine kinase (dCK) into active 2′,2′-difluorodeoxycytidine triphosphate (dFdCTP) metabolite. [6][7][8] However, GEM is a pyrimidine nucleoside analogue of deoxycytidine and can be catalyzed to 2′-deoxy-2′,2′-difluorouridine (dFdU), an inactive metabolite of GEM, by stromal and CDA.…”

Section: Introductionmentioning

confidence: 99%

Dihydroartemisinin increases gemcitabine therapeutic efficacy in ovarian cancer by inducing reactive oxygen species

Yang

Zhang

Shen

et al. 2018

J of Cellular Biochemistry

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Ovarian cancer is the major cause of death in women gynecological malignancy and gemcitabine (GEM) is commonly used in related chemotherapy. However, more than 90% GEM is catalyzed into an inactive metabolite 2'-deoxy-2',2'-difluorouridine by stromal and cellular cytidine deaminase (CDA). Dihydroartemisinin (DHA), which possesses an intramolecular endoperoxide bridge, could be activated by heme or ferrous iron to produce reactive oxygen species (ROS). The excess ROS generation will excite expression of heme oxygenase-1 and suppress CDA expression. Under low CDA expression, the inactivation of GEM is decreased in turn to exert excellent therapeutic efficiency. Herein, we first studied the ROS generation by DHA in vitro with A2780 cells by means of flow cytometry and confocal laser scanning microscopy. Furthermore, cytotoxicity assay in vitro showed that DHA + GEM had synergistic effect, with molar ratio of DHA and GEM at 10. Eventually, in A2780 ovarian cancer xenograft tumor model, DHA + GEM exhibited significant antitumor efficiency with lower blood toxicity than GEM alone. Noteworthy, the combination treatment group completely eliminated the tumors on day 14.

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Development and validation of a stability indicating isocratic HPLC method for gemcitabine with application to drug release from poly lactic-co-glycolic acid nanoparticles and enzymatic degradation studies

Abstract: These results demonstrate the utility and effectiveness of this simple isocratic HPLC method in evaluating the overall performance of a gemcitabine-loaded formulation.

Cited by 15 publications

References 27 publications

Formulation and Characterization of Glutathione-Loaded Bioadhesive Hydrogel for Ocular Delivery

Formulation and Characterization of Glutathione-Loaded Bioadhesive Hydrogel for Ocular Delivery

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Dihydroartemisinin increases gemcitabine therapeutic efficacy in ovarian cancer by inducing reactive oxygen species

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