Chrysin-loaded folate conjugated PF127-F68 mixed micelles with enhanced oral bioavailability and anticancer activity against human breast cancer cells

Baidya, Debjani; Kushwaha, Jeetendra; Mahadik, Kakasaheb R.; Patil, Sharvil

doi:10.1080/03639045.2019.1576726

Cited by 42 publications

(21 citation statements)

References 29 publications

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“…Despite its low water solubility, just a limited number of publications can be found focusing on the solubilization of chrysin. Folate-conjugated pluronic PF127-pluronic F68 mixed micelles [15], solid dispersions with surface active agents [16], and nanoparticles [17,18] were used to improve the bioavailability and effect of chrysin. Amino-appended cyclodextrins [19], SBECD [20], and βCD [21] were also used for the complex formation and solubilization of chrysin, but interestingly, the effect of cyclodextrins on the Caco-2 intestinal permeability of chrysin has not been studied yet.…”

Section: Discussionmentioning

confidence: 99%

Cyclodextrin Complexation Improves the Solubility and Caco-2 Permeability of Chrysin

et al. 2020

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Chrysin is a bioflavonoid that can be found in natural products such as honey and propolis, and it possesses several biological effects such as antioxidant, anti-inflammatory, and anti-cancer activity. However, it is poorly soluble in water, and its bioavailability is limited. The aim of this research is to investigate the chrysin solubilization capacity of different β-cylcodextrin derivatives and compare their biological activities. Chrysin was complexed with β-cyclodextrin (βCD), hydroxypropyl-β-, (HPBCD) sulfobutylether-β-, (SBECD), and randomly-methylated-β-cyclodextrin (RAMEB) by the lyophilization method in 1:1 and 1:2 molar ratios. The solubilities of the chrysin–cyclodextrin complexes were tested, and the solubilization abilities of cyclodextrins were studied by phase solubility experiments. The cytotoxicity of the complexes was measured by the MTT method, and the permeability enhancement was tested on Caco-2 monolayers. The solubility study showed that the complexes formed with RAMEB had the highest solubility in water. The phase solubility experiments confirmed the strongest interaction between RAMEB and chrysin. In the viability test, none of the complexes showed cytotoxicity up to 100 µM concentration. The permeability study revealed that both at 1:1 and 1:2 ratios, the RAMEB complexes were the most effective to enhance chrysin permeability through the Caco-2 monolayers. In conclusion, cyclodextrins, especially RAMEB, are suitable for improving chrysin solubility and absorption.

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Section: Discussionmentioning

confidence: 99%

Cyclodextrin Complexation Improves the Solubility and Caco-2 Permeability of Chrysin

et al. 2020

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“…Additionally, PCL-PEG nanoparticles (without drug) were non-toxic in the liver and kidney of mice (49). Several researches reported that polymer could improve the bioavailability of chrysin (33,50).…”

Section: Introductionmentioning

confidence: 99%

Upregulation of G Protein-Coupled Estrogen Receptor by Chrysin-Nanoparticles Inhibits Tumor Proliferation and Metastasis in Triple Negative Breast Cancer Xenograft Model

Kim

Jung

2020

Front. Endocrinol.

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Triple-negative breast cancer (TNBC) is associated with a high mortality rate among women globally. TNBC shows a high rate of recurrence and distant metastasis. Particularly, the chemotherapy is limited because hormone therapy of breast cancer is ineffective. Thus, an effective chemotherapeutic agent is needed for tumor suppression. Chrysin-nanoparticles (chrysin-NPs) were investigated for their inhibitory effect on a MDA-MB-231-derived xenograft model. To gain insight into the underlying mechanisms, we conducted human matrix metalloproteinase (MMP) array, western blot, and immunohistochemistry analysis. Furthermore, in vivo imaging was used to monitor the chemotherapeutic efficacy of chrysin-NPs in a metastasis mouse model. Chrysin-NPs significantly inhibited the proliferation of MDA-MB-231 cells via the PI3K/JNK pathway and induced cell death through the p53-apoptosis pathway, leading to delayed MDA-MB-231-derived tumor growth. Interestingly, chrysin-NPs significantly induced G protein-coupled estrogen receptor (GPER) expression, which suppresses MMPs and NF-κB expression. Chrysin-NPs acted as effective metastasis inhibitors. Our results suggest that chrysin-NPs may be used as an effective adjuvant formulation to inhibit TNBC progression.

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“…According to the guideline of Biopharmaceutics Classification System (BCS) from the Food and Drug Administration (FDA), water solubility and permeability of active ingredients are major indexes that govern drug absorption and therefore are directly related to bioavailability [33]. Most compounds from products of Nature are BCS class II or IV, such as quercetin [34], resveratrol [35] and chrysin [36], and their poor water solubility may limit their absorption, resulting in reduction of biological activity. Our present study indicated that 734THIF, which belongs to BCS class II or IV, has poor water solubility, which might influence its pharmaceutical effect.…”

Section: Discussionmentioning

confidence: 99%

Improvement of Skin Penetration, Antipollutant Activity and Skin Hydration of 7,3′,4′-Trihydroxyisoflavone Cyclodextrin Inclusion Complex

Huang

Yen

et al. 2019

Pharmaceutics

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As is known, many antioxidants from plant extracts have been used as additives in skincare products to prevent skin damage following overexposure to environmental pollutants. 7,3′,4′-trihydroxyisoflavone (734THIF), an isoflavone compound, possesses various biological activities, including antioxidant, antityrosinase, photodamage protection, and anticancer effects. Unfortunately, 734THIF has poor water solubility, which limits its skin penetration and absorption, and subsequently influences its biological activity. The aim of the present study was to investigate the mechanisms for the improvement in water solubility and skin penetration of 2-hydroxypropyl-β-cyclodextrin (HPBCD) inclusion complex with 734THIF (5-7HP). We also determined its photostability, antipollutant activity in HaCaT keratinocytes, and moisturizing effect in human subjects. Our results showed that 734THIF was embedded into the lipophilic inner cavity of HPBCD and its water solubility and skin penetration were thereby improved through amorphous transformation, surface area enhancement, and hydrogen bonding formation between 734THIF and HPBCD. In addition, 5-7HP inhibited PM-induced ROS generation and then downregulated ROS-mediated COX-2 and MMP9 production and AQP-3 consumption by inhibiting the phosphorylation of MAPKs. Consequently, we suggest that 5-7HP is a safe and photostable topical ingredient to enhance the skin penetration of 734THIF and skin hydration, and therefore 5-7HP may be used as an antipollutant additive in skin care products.

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Chrysin-loaded folate conjugated PF127-F68 mixed micelles with enhanced oral bioavailability and anticancer activity against human breast cancer cells

Cited by 42 publications

References 29 publications

Cyclodextrin Complexation Improves the Solubility and Caco-2 Permeability of Chrysin

Cyclodextrin Complexation Improves the Solubility and Caco-2 Permeability of Chrysin

Upregulation of G Protein-Coupled Estrogen Receptor by Chrysin-Nanoparticles Inhibits Tumor Proliferation and Metastasis in Triple Negative Breast Cancer Xenograft Model

Improvement of Skin Penetration, Antipollutant Activity and Skin Hydration of 7,3′,4′-Trihydroxyisoflavone Cyclodextrin Inclusion Complex

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