Preparation and characterization of micronized ellagic acid using antisolvent precipitation for oral delivery

Li, Yong; Zhao, Xiuhua; Zu, Yuangang; Zhang, Yin; Ge, Yunshan; Chen, Zhong; Wei, Weiwei

doi:10.1016/j.ijpharm.2015.03.071

Cited by 35 publications

(34 citation statements)

References 47 publications

(52 reference statements)

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“…Although, the improved bioavailability of EA was monitored with micro-crystallization by Li et al when they used anti-solvent precipitation technique by dissolving EA in N-methyl pyrrolidone followed by precipitation in deionized water. 46 In this study, we have concluded that the nano-encapsulation of EA in PCL matrix led to the enhancement of its oral bioavailability. The orally administered NPs were absorbed via special mucosa-associated M-cells of the lymphoid cells located in small intestine (Peyer's patches).…”

mentioning

confidence: 74%

Enhanced anticancer activity and oral bioavailability of ellagic acid through encapsulation in biodegradable polymeric nanoparticles

Mady¹,

Shaker²

2017

IJN

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Despite the fact that various studies have investigated the clinical relevance of ellagic acid (EA) as a naturally existing bioactive substance in cancer therapy, little has been reported regarding the efficient strategy for improving its oral bioavailability. In this study, we report the formulation of EA-loaded nanoparticles (EA-NPs) to find a way to enhance its bioactivity as well as bioavailability after oral administration. Poly(ε-caprolactone) (PCL) was selected as the biodegradable polymer for the formulation of EA-NPs through the emulsion–diffusion–evaporation technique. The obtained NPs have been characterized by measuring particle size, zeta potential, Fourier transform infrared, differential scanning calorimetry, and X-ray diffraction. The entrapment efficiency and the release profile of EA was also determined. In vitro cellular uptake and cytotoxicity of the obtained NPs were evaluated using Caco-2 and HCT-116 cell lines, respectively. Moreover, in vivo study has been performed to measure the oral bioavailability of EA-NPs compared to free EA, using New Zealand white rabbits. NPs with distinct shape were obtained with high entrapment and loading efficiencies. Diffusion-driven release profile of EA from the prepared NPs was determined. EA-NP-treated HCT-116 cells showed relatively lower cell viability compared to free EA-treated cells. Fluorometric imaging revealed the cellular uptake and efficient localization of EA-NPs in the nuclear region of Caco-2 cells. In vivo testing revealed that the oral administration of EA-NPs produced a 3.6 times increase in the area under the curve compared to that of EA. From these results, it can be concluded that incorporation of EA into PCL as NPs enhances its oral bioavailability and activity.

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mentioning

confidence: 74%

Enhanced anticancer activity and oral bioavailability of ellagic acid through encapsulation in biodegradable polymeric nanoparticles

Mady¹,

Shaker²

2017

IJN

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“…In regard to the EA dose associated with in vivo anticancer properties, it appears largely higher than that administered as dietary supplement in humans. It should be noted that EA pharmacokinetics is quite unfavorable, due to low bioavailability as a result of poor absorption, metabolism by intestinal microorganism and short plasma half-life [45,46]. Nevertheless, future development of EA derivatives or formulations with improved pharmacokinetics may allow to better define the dose-effect relationship and to reduce the amount of the active principle to be administered in patients by systemic or local routes.…”

Section: Discussionmentioning

confidence: 99%

Ellagic Acid Inhibits Bladder Cancer Invasiveness and In Vivo Tumor Growth

et al. 2016

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Ellagic acid (EA) is a polyphenolic compound that can be found as a naturally occurring hydrolysis product of ellagitannins in pomegranates, berries, grapes, green tea and nuts. Previous studies have reported the antitumor properties of EA mainly using in vitro models. No data are available about EA influence on bladder cancer cell invasion of the extracellular matrix triggered by vascular endothelial growth factor-A (VEGF-A), an angiogenic factor associated with disease progression and recurrence, and tumor growth in vivo. In this study, we have investigated EA activity against four different human bladder cancer cell lines (i.e., T24, UM-UC-3, 5637 and HT-1376) by in vitro proliferation tests (measuring metabolic and foci forming activity), invasion and chemotactic assays in response to VEGF-A and in vivo preclinical models in nude mice. Results indicate that EA exerts anti-proliferative effects as a single agent and enhances the antitumor activity of mitomycin C, which is commonly used for the treatment of bladder cancer. EA also inhibits tumor invasion and chemotaxis, specifically induced by VEGF-A, and reduces VEGFR-2 expression. Moreover, EA down-regulates the expression of programmed cell death ligand 1 (PD-L1), an immune checkpoint involved in immune escape. EA in vitro activity was confirmed by the results of in vivo studies showing a significant reduction of the growth rate, infiltrative behavior and tumor-associated angiogenesis of human bladder cancer xenografts. In conclusion, these results suggest that EA may have a potential role as an adjunct therapy for bladder cancer.

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“…Li et al set the best conditions to produce m-EA by anti-solvent precipitation with an accurate preformulative study [51]. An EA solution in NMP (30 mg/mL) was added to water, used as antisolvent, at a rate of 30 mL/h with 2 min precipitation time, at 3 °C and 2500 rpm stirring.…”

Section: Micronized Ea (M-ea)mentioning

confidence: 99%

Formulation Strategies to Improve Oral Bioavailability of Ellagic Acid

Zuccari¹,

Baldassari²,

Ailuno³

et al. 2020

Preprint

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Featured Application: An updated description of pursued approaches for efficiently resolving the low bioavailability issue of ellagic acid. Abstract: Ellagic acid, a polyphenolic compound present in fruits and berries, has recently been object of extensive research for its antioxidant activity, which might be useful for the prevention and treatment of cancer, cardiovascular pathologies, and neurodegenerative disorders. Its protective role justifies numerous attempts to include it in functional food preparations and in dietary supplements not only to limit the unpleasant collateral effects of chemotherapy. However, ellagic acid use as chemopreventive agent has been debated because of its poor bioavailability associated to low solubility, limited permeability, first pass effect, and interindividual variability in gut microbial transformations. To overcome these drawbacks, various strategies for oral administration including solid dispersions, micro-nanoparticles, inclusion complexes, selfemulsifying systems, polymorphs have been proposed. Here, we have listed an updated description of pursued micro/nanotechnological approaches focusing on the fabrication processes and the features of the obtained products, as well as on the positive results yielded by in vitro and in vivo studies in comparison to the raw material. The micro/nano-sized formulations here described might be exploited for pharmaceutical delivery of this active, as well as for the production of nutritional supplements or for the enrichment of novel foods.

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Preparation and characterization of micronized ellagic acid using antisolvent precipitation for oral delivery

Cited by 35 publications

References 47 publications

Enhanced anticancer activity and oral bioavailability of ellagic acid through encapsulation in biodegradable polymeric nanoparticles

Enhanced anticancer activity and oral bioavailability of ellagic acid through encapsulation in biodegradable polymeric nanoparticles

Ellagic Acid Inhibits Bladder Cancer Invasiveness and In Vivo Tumor Growth

Formulation Strategies to Improve Oral Bioavailability of Ellagic Acid

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