Enhanced growth inhibition effect of Resveratrol incorporated into biodegradable nanoparticles against glioma cells is mediated by the induction of intracellular reactive oxygen species levels

Shao, Jianghua; Li, Xin; Lu, Xiaowei; Jiang, Chen; Hu, Yong; Li, Qingping; You, Yongping; Fu, Zhen-Yan

doi:10.1016/j.colsurfb.2009.03.010

Cited by 149 publications

(96 citation statements)

References 12 publications

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“…[1][2][3] However, in most studies resveratrol has been used in its free form, which is not suitable for drug delivery. Nanocarriers have rarely been considered, [4][5][6][7][8][9] thus presenting a challenge still to be pursued. The development of site-specific drug delivery systems that protect resveratrol during its transit inside the organism is extremely important to preserve its pharmacological properties, while enhancing its bioavailability after oral administration.…”

Section: Introductionmentioning

confidence: 99%

Novel resveratrol nanodelivery systems based on lipid nanoparticles to enhance its oral bioavailability

Neves¹,

Lúcio²,

Martins³

et al. 2013

IJN

133

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Introduction:Resveratrol is a polyphenol found in grapes and red wines. Interest in this polyphenol has increased due to its pharmacological cardio-and neuroprotective, chemopreventive, and antiaging effects, among others. Nevertheless, its pharmacokinetic properties are less favorable, since the compound has poor bioavailability, low water solubility, and is chemically unstable. To overcome these problems, we developed two novel resveratrol nanodelivery systems based on lipid nanoparticles to enhance resveratrol's oral bioavailability for further use in medicines, supplements, and nutraceuticals. Methods and materials: Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) loaded with resveratrol were successfully produced by a modified hot homogenization technique. These were completely characterized to evaluate the quality of the developed resveratrol-loaded nanoparticles. Results: Cryo-scanning electron microscopy morphology studies showed spherical and uniform nanoparticles with a smooth surface. An average resveratrol entrapment efficiency of ∼70% was obtained for both SLNs and NLCs. Dynamic light scattering measurements gave a Z-average of 150-250 nm, polydispersity index of ∼0.2, and a highly negative zeta potential of around −30 mV with no statistically significant differences in the presence of resveratrol. These characteristics remained unchanged for at least 2 months, suggesting good stability. Differential scanning calorimetry studies confirmed the solid state of the SLNs and NLCs at both room and body temperatures. The NLCs had a less ordered crystalline structure conferred by the inclusion of the liquid lipid, since they had lower values for phase transition temperature, melting enthalpy, and the recrystallization index. The presence of resveratrol induced a disorder in the crystal structure of the nanoparticles, suggesting a favoring of its entrapment. The in vitro release studies on conditions of storage showed a negligible resveratrol release over several hours for both nanosystems and the in vitro simulation of gastrointestinal transit showed that the resveratrol remained mostly associated with the lipid nanoparticles after their incubation in digestive fluids. Conclusion: Both nanodelivery systems can be considered suitable carriers for oral administration, conferring protection to the incorporated resveratrol and allowing a controlled release after uptake.

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Section: Introductionmentioning

confidence: 99%

Novel resveratrol nanodelivery systems based on lipid nanoparticles to enhance its oral bioavailability

Neves¹,

Lúcio²,

Martins³

et al. 2013

IJN

133

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“…In particular, RSV incorporation into mPEG-poly(ε-caprolactone)-based NPs resulted in significantly higher cytotoxicity against malignant glioma cells compared to an equivalent dose of free biomolecule. 32 Solid-lipid NPs loaded with RSV also contributed to effectiveness of RSV on decreasing cell proliferation and demonstrated potential benefits for prevention of skin cancer. 33 Moreover, other authors investigated the effect of RSV incorporated in liposome on the proliferation and ultraviolet B (UVB) protection of cells, in order to enhance the efficacy in the prevention and treatment of human skin disorders caused by excessive exposure to UV radiation.…”

Section: Introductionmentioning

confidence: 99%

Development of novel cationic chitosan- and anionic alginate–coated poly(D,L-lactide-co-glycolide) nanoparticles for controlled release and light protection of resveratrol

Sanna¹,

Roggio²,

Siliani³

et al. 2012

IJN

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Background:Resveratrol, like other natural polyphenols, is an extremely photosensitive compound with low chemical stability, which limits the therapeutic application of its beneficial effects. The development of innovative formulation strategies, able to overcome physicochemical and pharmacokinetic limitations of this compound, may be achieved via suitable carriers able to associate controlled release and protection. In this context, nanotechnology is proving to be a powerful strategy. In this study, we developed novel cationic chitosan (CS)-and anionic alginate (Alg)-coated poly(d,l-lactide-co-glycolide) nanoparticles (NPs) loaded with the bioactive polyphenolic trans-(E)-resveratrol (RSV) for biomedical applications. Methods: NPs were prepared by the nanoprecipitation method and characterized in terms of morphology, size and zeta potential, encapsulation efficiency, Raman spectroscopy, swelling properties, differential scanning calorimetry, and in vitro release studies. The protective effect of the nanosystems under the light-stressed RSV and long-term stability were investigated. Results: NPs turned out to be spherical in shape, with size ranging from 135 to about 580 nm, depending on the composition and the amount of polyelectrolytes, while the encapsulation efficiencies increased from 8% of uncoated poly(d,l-lactide-co-glycolide) (PLGA) to 23% and 32% of Alg-and CS-coated PLGA NPs, respectively. All nanocarriers are characterized by a biphasic release pattern, and more effective controlled release rates are obtained for NPs formulated with higher polyelectrolyte concentrations. Stability studies revealed that encapsulation provides significant protection against light-exposure degradation, by reducing the trans-cis photoisomerization reaction. Moreover, the nanosystems are able to prevent the degradation of trans isoform and the leakage of RSV from the carrier for a period of 6 months. Conclusion: Our findings indicated that the newly developed CS-and Alg-coated PLGA NPs are suitable to be used for the delivery of bioactive RSV. The encapsulation of RSV into optimized polymeric NPs provides improved drug loading, effective controlled release, and protection against light-exposure degradation, thus opening new perspectives for the delivery of bioactive related phytochemicals to be used for (nano)chemoprevention/chemotherapy.

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“…Regarding the loading efficiency, it depends mainly on the lipophilicity of RSV and its affinity to the hydrophobic core (PCL). The highest drug loading content of RSV into polymeric nanoparticles was about 20% and the encapsulation efficiency was 90% [75,76]. The cellular uptake of the polymeric nanoparticles occurs by endocytosis, which enhances the drug penetration in cells and demonstrates higher therapeutic efficiency than the obtained with free drug administration.…”

Section: Rsv Delivery Systemsmentioning

confidence: 96%

Reduction of Hepatotoxicity Induced by Doxorubicin

Bengaied¹,

Ribeiro²,

Amri³

et al. 2017

J Integr Oncol

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Doxorubicin (DOX) has been used in the treatment of variety of cancers but its administration is limited by a dosedependent toxicity. Its cytotoxic effects on malignant cells have shown an increase in the risk of cardiotoxicity, hepatoxicity, renal insufisance.Antioxydants have been explored for both their cancer preventive properties and chemodulatory of DOX toxicity. Resveratrol (RSV) is a polyphenolic constituent of several dietary mainly of grapes and wine origin recently its anticancer potential has been extensively explored, revealing its anti-proliferative effect on different cancer cell lines, both in vitro and in vivo. RSV is also known to have modulatory effects on cell apoptosis, migration and growth via various signaling pathways. Though, RSV possesses great medicinal value, its applications as a therapeutic drug is limited. Problems like low oral bioavailability and poor aqueous solubility make RSV an unreliable candidate for therapeutic purposes. Additionally, the rapid gastrointestinal digestion of RSV is also a major barrier for its clinical translation. Hence, to overcome these disadvantages RSV-based nanodelivery systems have been considered in recent times. Nanodelivery systems of RSV have shown promising results in its uptake by the epithelial system as well as enhanced delivery to the target site. Herein we have tried to bring new new insights into the molecular mechanisms of DOX toxicity with respect to DNA damage, free radicals and whether RSV can be a playmaker as chemodulatory of DO x .

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Enhanced growth inhibition effect of Resveratrol incorporated into biodegradable nanoparticles against glioma cells is mediated by the induction of intracellular reactive oxygen species levels

Cited by 149 publications

References 12 publications

Novel resveratrol nanodelivery systems based on lipid nanoparticles to enhance its oral bioavailability

Novel resveratrol nanodelivery systems based on lipid nanoparticles to enhance its oral bioavailability

Development of novel cationic chitosan- and anionic alginate–coated poly(D,L-lactide-co-glycolide) nanoparticles for controlled release and light protection of resveratrol

Reduction of Hepatotoxicity Induced by Doxorubicin

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Enhanced growth inhibition effect of Resveratrol incorporated into biodegradable nanoparticles against glioma cells is mediated by the induction of intracellular reactive oxygen species levels

Cited by 149 publications

References 12 publications

Novel resveratrol nanodelivery systems based on lipid nanoparticles to enhance its oral bioavailability

Novel resveratrol nanodelivery systems based on lipid nanoparticles to enhance its oral bioavailability

Development of novel cationic chitosan- and anionic alginate&ndash;coated poly(D,L-lactide-co-glycolide) nanoparticles for controlled release and light protection of resveratrol

Reduction of Hepatotoxicity Induced by Doxorubicin

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Development of novel cationic chitosan- and anionic alginate–coated poly(D,L-lactide-co-glycolide) nanoparticles for controlled release and light protection of resveratrol