In vitro and in vivo evaluation of enzymatic and antioxidant activity, cytotoxicity and genotoxicity of curcumin-loaded solid dispersions

Sá, Igor Silva de; Perón, Ana Paula; Leimann, Fernanda Vitória; Bressan, Getúlio Nicola; Krum, Bárbara Nunes; Fachinetto, Roselei; Pinela, José; Calhelha, Ricardo C.; Barreiro, María Filomena; Ferreira, Isabel C.F.R.; Gonçalves, Odinei Hess; Ineu, Rafael Porto

doi:10.1016/j.fct.2018.12.037

Cited by 54 publications

(21 citation statements)

References 51 publications

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“…Recently, curcumin SDs were obtained using Poloxamer 407 as the encapsulant agent and their cytotoxic effects were evaluated against tumoral (breast, lung, cervical and hepatocellular carcinoma) and PLP2 non-tumoral cells. These formulations that were readily dispersible in water had cytotoxicity against all the tested tumor cell lines without toxic effects for non-tumor cells [234].…”

Section: Curcumin/β-cyclodextrin and Solid Dispersions Formulationsmentioning

confidence: 99%

“…β-CD + CUR Superior sunlight stability and solubility respect to pure colourant [218] Liquid-type β-CD + CUR Improved solubility in water and bioavailability [220,221] Solid type β-CD + CUR Improved storage stability and biovailability [222] CUR-CD-CS Superior solubility, cellular absorption and antitumor effects compared to free curcumin in skin cancer cells [223] β-CD + CUR Improved uptake and therapeutic efficacy in prostate cancer cells [154] β-CD + CUR Improved delivery and therapeutic efficacy compared to free curcumin in both in vitro lung carcinoma cell lines and in vivo mouse hepatoma xenograft models [224] β-CD + CUR Superior anticancer effects respect to free curcumin in cervical cancer cells [225] FA-CUR-NPs Improved drug release rate, cellular uptake efficiency and in vitro and in vivo antitumor activity respect to free curcumin in cervical cancer cells [226] Hydroxypropyl-β-CD+ CUR+piperine Improved solubility of the curcumin-piperine system, its permeability through biological membranes, antioxidant and antimicrobial activities and enzymatic inhibition [227] SDs (with Gelucire ® 50/13-Aerosil) + CUR Improved stability, water solubility, dissolution rate, bioavailability and anti-inflammatory activity in rats [229] Solutol ® HS15 SDs + CUR Improved solubility and bioavailability compared to free curcumin [231] SDs (with cellulose acetate and mannitol) + CUR Improved water solubility and oral bioavailability compared to free curcumin [232] SDs + CUR Superior water solubility and gastrointestinal absorption in rats [233] SDs (with Poloxamer 407) + CUR Improved water dispersibility and cytotoxic effects against breast, lung, cervical and hepatocellular cancer cells [234] Curcumin Conjugates Formulations Piperine + CUR Curcumin enhanced serum levels, reduced elimination half-life and clearance, increased bioavailability in rats and humans [236] Piperine + CUR Curcumin increased bioavailability in epileptic rats [237] Piperine + CUR Curcumin enhanced intestinal absorption and bioavailability in rats [238] BCM-95CG (Biocurcumax ® ): piperine + lecithin + CUR Curcumin improved bioavailability and pharmacokinetic profile respect to free drug in healthy subjects [239]…”

Section: Composition Outcomes Referencesmentioning

confidence: 99%

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Antitumoral Activities of Curcumin and Recent Advances to ImProve Its Oral Bioavailability

et al. 2021

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Curcumin, a main bioactive component of the Curcuma longa L. rhizome, is a phenolic compound that exerts a wide range of beneficial effects, acting as an antimicrobial, antioxidant, anti-inflammatory and anticancer agent. This review summarizes recent data on curcumin’s ability to interfere with the multiple cell signaling pathways involved in cell cycle regulation, apoptosis and the migration of several cancer cell types. However, although curcumin displays anticancer potential, its clinical application is limited by its low absorption, rapid metabolism and poor bioavailability. To overcome these limitations, several curcumin-based derivatives/analogues and different drug delivery approaches have been developed. Here, we also report the anticancer mechanisms and pharmacokinetic characteristics of some derivatives/analogues and the delivery systems used. These strategies, although encouraging, require additional in vivo studies to support curcumin clinical applications.

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Section: Curcumin/β-cyclodextrin and Solid Dispersions Formulationsmentioning

confidence: 99%

Section: Composition Outcomes Referencesmentioning

confidence: 99%

Antitumoral Activities of Curcumin and Recent Advances to ImProve Its Oral Bioavailability

et al. 2021

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“…There are currently several nanoencapsulation techniques, but ionic gelation and antisolvent precipitation are in vogue. The products used for nanoformulations currently include: liposomes, polymers, nanoparticles, conjugates, solid dispersions, cyclodextrins, micelles, nanospheres and microcapsules and other various nanoformulations [42,90,91].…”

Section: Breast Cancermentioning

confidence: 99%

Latest Innovations and Nanotechnologies with Curcumin as a Nature-Inspired Photosensitizer Applied in the Photodynamic Therapy of Cancer

Ailioaie

Litscher

2021

Pharmaceutics

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In the context of the high incidence of cancer worldwide, state-of-the-art photodynamic therapy (PDT) has entered as a usual protocol of attempting to eradicate cancer as a minimally invasive procedure, along with pharmacological resources and radiation therapy. The photosensitizer (PS) excited at certain wavelengths of the applied light source, in the presence of oxygen releases several free radicals and various oxidation products with high cytotoxic potential, which will lead to cell death in irradiated cancerous tissues. Current research focuses on the potential of natural products as a superior generation of photosensitizers, which through the latest nanotechnologies target tumors better, are less toxic to neighboring tissues, but at the same time, have improved light absorption for the more aggressive and widespread forms of cancer. Curcumin incorporated into nanotechnologies has a higher intracellular absorption, a higher targeting rate, increased toxicity to tumor cells, accelerates the activity of caspases and DNA cleavage, decreases the mitochondrial activity of cancer cells, decreases their viability and proliferation, decreases angiogenesis, and finally induces apoptosis. It reduces the size of the primary tumor, reverses multidrug resistance in chemotherapy and decreases resistance to radiation therapy in neoplasms. Current research has shown that the use of PDT and nanoformulations of curcumin has a modulating effect on ROS generation, so light or laser irradiation will lead to excessive ROS growth, while nanocurcumin will reduce the activation of ROS-producing enzymes or will determine the quick removal of ROS, seemingly opposite but synergistic phenomena by inducing neoplasm apoptosis, but at the same time, accelerating the repair of nearby tissue. The latest curcumin nanoformulations have a huge potential to optimize PDT, to overcome major side effects, resistance to chemotherapy, relapses and metastases. All the studies reviewed and presented revealed great potential for the applicability of nanoformulations of curcumin and PDT in cancer therapy.

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“…4,6,7 Phenolic hydroxyl in the molecular structure of CUR was generally conjugated with small or large molecules containing carboxyl group in order to improve its anti-tumor activity, 8,9 drug stability and pharmacokinetic behavior. 10 The design of dosage form was another approach to change the physicochemical properties of CUR, such as nanoemulsions, 11 nanoparticles, 12 polymer micelles, 13 solid dispersions, 14 liposomes, 15 microspheres and microcapsules, 16 in situ gels. 17 However, CUR loaded nanocarriers have the deficiencies of low drug loading, easy leakage, uncontrollable drug release and quick elimination in vivo.…”

Section: Introductionmentioning

confidence: 99%

Excogitation and Assessment of Curcumin-Vitamin E Self-assembly PEGylated Nanoparticles by the Route of Oral Administration

Huang

Chen

Liu

et al. 2021

Journal of Pharmaceutical Sciences

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Curcumin (CUR) has attracted wide research interests due to its abundant bioactivities and potential advantages in cancer treatment. But the poor water solubility, instability, and quick metabolization and elimination after oral administration severely restrict the efficacy and further clinical application of CUR. Derivation is an approach often used to improve the druggability of active ingredients, so the study aim to prepare a CUR derivate with better stability, satisfactory pharmacokinetics, and inherent selfassembled ability in contrast with CUR. The derivate was designed and evaluated in vitro and in vivo. Vitamin E (VE) was used to perform the esterification reaction with CUR, and the cytotoxicity of derivative CUR-VE ester on MCF-7 tumor cells was similar to CUR. Besides the better stability in simulated gastric and intestinal fluid, plasma and liver homogenate, the self-assembly CUR-VE nanoparticles were fabricated by feasible and controllable nanoprecipitation method. The Transmission Electron Microscope (TEM) showed CUR-VE NPs were spherical with an average particle size of 172.9 nm, and drug loading was up to 93%. CUR-VE NPs exhibited a sustained-release behavior and fitted to Fick's diffusion mechanism. Differential Scanning Calorimeter (DSC), X-ray Powder Diffractometer (XRPD) and Fourier Transform Infrared Spectrometer (FTIR) declared no crystalline substances were formed, and the selfassembly process of CUR-VE relied on driving forces including van der Waals forces, hydrogen bonding forces, intermolecular forces. In pharmacokinetics, C max and AUC 0-∞ of CUR-VE NPs by the route of oral administration were (104.69 ± 40.72) ng/mL and (3496.92 ± 1088.93) ng/mL*h, which were about three times and 18 times more compared with CUR. The eliminated half-time of CUR-VE extended to 28 h ascribed to the outstanding stability and surface PEGylation of NPs. It prompted that appropriately PEGylated NPs via oral administration was beneficial to prolong systemic circulation similar to intravenous PEGylated NPs.In summary, the study provides a convenient way to fabricate the self-assembled CUR-VE NPs qualified with high drug loading, satisfactory stability and desired pharmacokinetics. CUR-VE has the potent advantage to be an ideal substitute for CUR in the future of healthcare and clinical application.

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In vitro and in vivo evaluation of enzymatic and antioxidant activity, cytotoxicity and genotoxicity of curcumin-loaded solid dispersions

Cited by 54 publications

References 51 publications

Antitumoral Activities of Curcumin and Recent Advances to ImProve Its Oral Bioavailability

Antitumoral Activities of Curcumin and Recent Advances to ImProve Its Oral Bioavailability

Latest Innovations and Nanotechnologies with Curcumin as a Nature-Inspired Photosensitizer Applied in the Photodynamic Therapy of Cancer

Excogitation and Assessment of Curcumin-Vitamin E Self-assembly PEGylated Nanoparticles by the Route of Oral Administration

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