Design, Preparation and Evaluation of Supramolecular Complexes with Curcumin for Enhanced Cytotoxicity in Breast Cancer Cell Lines

Abdelkader, Hamdy; Fatease, Adel Al; Fathalla, Zeinab; Shoman, Mai E.; Abou-Taleb, Heba A; Abourehab, Mohammed A. S.

doi:10.3390/pharmaceutics14112283

Cited by 4 publications

(4 citation statements)

References 26 publications

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“…Molecular docking recorded binding constants of −5.908 and −6.357 for imipenem:β-CD and imipenem:HP β-CD, respectively. These binding constants can ensure inclusion complexation and have been confirmed elsewhere using thermal and spectral analyses [26,34].…”

Section: Discussionsupporting

confidence: 55%

“…Both physical mixing and kneading methods were adopted to prepare imipene clodextrins (CDs) complexes. These two methods are frequently utilized to create sion complexes of active pharmaceutical ingredients (APIs) and cyclodextrins [25 two methods do not involve heat or extreme freezing; nevertheless, the complexes c formed at ambient conditions [26,27].…”

Section: Resultsmentioning

confidence: 99%

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Comparative Investigation into the Roles of Imipenem:Cyclodextrin Complexation and Antibiotic Combination in Combatting Antimicrobial Resistance in Gram-Negative Bacteria

Farhan,

El-Baky,

Ahmed

et al. 2023

Pharmaceuticals

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Extensively drug-resistant (XDR), multidrug-resistant (MDR) and pandrug-resistant (PDR) Gram-negative microorganisms (GNBs) are considered a significant global threat. β-lactam and aminoglycoside combinations and imipenem:cyclodextrin inclusion complexes were studied for the treatment of lethal GNBs. This is because of the broad empiric coverage of the two drugs and their possession of different spectra of activity. Two cyclodextrins (β- and hydroxy propyl β-cyclodextrins) were utilized for inclusion complex formation with imipenem using the physical and kneading methods. In silico investigation using the molecular docking and Fourier-infrared spectroscopy (FTIR) were employed to estimate binding constant and confirm complex formation, respectively. The in vitro effects of amikacin and imipenem combination in comparison to the effect of imipenem-β- and hydroxy propyl β-cyclodextrin (CD) complexes against Klebsiella spp. and Acinetobacter baumannii were studied. The isolated microorganisms’ antimicrobial responsiveness to various antibiotics (19 antibiotics) was evaluated. It was found that piperacillin/tazobactam and gentamycin (resistance rates were 33.3% and 34%, respectively) were the most effective antimicrobials. The in vitro studies have been performed by the checkerboard technique and time-killing assay. The studied combination of amikacin and imipenem showed a substantial drop in bacterial count (p < 0.05). The in vitro studies demonstrated a synergism for the investigated combination. Conventional PCR was used in molecular studies to identify the resistance genes bla IMP and aac (6′)-Ib. The blaIMP and aac (6′)-Ib were recorded in 38.2% and 3.6% of the studied isolates, respectively. The in vitro studies showed synergistic effects among the tested antibiotics with FICIs of ≤0.5. Finally, the study compared the reduction in bacterial count between the tested antibiotic combinations and imipenem:CD physical and kneaded mixtures. Imipenem:CD inclusion complexes demonstrated a significant bacterial count reduction over the antibiotic combination. These results highlight the emerging role of CDs as safe biofunctional excipients in the combat against superbug bacterial resistance.

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Section: Discussionsupporting

confidence: 55%

Section: Resultsmentioning

confidence: 99%

Comparative Investigation into the Roles of Imipenem:Cyclodextrin Complexation and Antibiotic Combination in Combatting Antimicrobial Resistance in Gram-Negative Bacteria

Farhan,

El-Baky,

Ahmed

et al. 2023

Pharmaceuticals

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“…The formed complex alters the physiochemical characteristics of the guest, in particular to enhance water solubility (38). Inclusion complexes with CDs have been successfully used for preparation of commercially available pharmaceuticals to enhance the solubility (39)(40)(41)(42).…”

Section: Introductionmentioning

confidence: 99%

Interactions of Cyclodextrins and their Hydroxyl Derivatives with Etodolac: Solubility and Dissolution Enhancement

Mustafa¹,

Khoder

Abdelkader

et al. 2024

CDD

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Background: Poor solubility and dissolution rate of drugs are largely responsible for erratic drug absorption and limited oral bioavailability. Etodolac (ETO) is a non-steroidal anti-inflammatory drug (NSAID) that is classified as BCS class II (dissolution rate-dependent absorption). ETO has high safety and efficacy in pain relief and control of inflammation. ETO is commercially available as (400-600 mg) tablets; poor solubility and dissolution rate of ETO could result in variable oral absorption and inconsistent analgesic responses. The aim of this study was to improve solubility and dissolution rates of ETO by complexation with cyclodextrins (CDs). Methods: Four different CDs namely β-, γ-, HP β-CDs, and HP γ-CDs were prepared using three different methods; solvent evaporation (CO), freeze-drying (FD), and physical mixing (PM). The prepared drug: excipient mixtures were investigated for aqueous solubility, as well as via DSC, XRD, FTIR, SEM, dissolution, and docking. Results: The results revealed a solubility phase diagram of the AL type, indicating a 1:1 complexation of ETO: CD. These results agreed with our molecular docking calculations. DSC, FTIR, XRD, and SEM results confirmed the formation of an inclusion complex. The complexation efficiency, solubility, and dissolution enhancement were in the order of HPγ-CD > γ-CD > HPβ-CD > β-CD. FD method was superior to both CO and PM. Conclusion: Superior dissolution enhancements of ETO were recorded for the FD mixture (up to 90% dissolved in less than 10 min). In conclusion, γ- and hydroxypropyl γ-derivative of cyclodextrins can be considered a promising excipient for enhancement of dissolution rates concerned for ETO.

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“…[1] Abdelkader et at. (2022) [33] Ismail-Alhasawi (2022) [34] Fawzy et al On the other hand, an additional approach to solving the problem of poor solubility of curcuminoid-type molecules has been the discovery of new formulations, including liposomes [39,40], nanoparticles [41][42][43][44][45], or the preparation of inclusion complexes with cyclodextrins [46,47]. Beta-cyclodextrin (BCD) is the first choice [48] for the administration of drugs toward their sites of action because of its low toxicity [49], certain hydrophilicity [50], and adequate cavity.…”

Section: Introductionmentioning

confidence: 99%

The Antitumoral Effect In Ovo of a New Inclusion Complex from Dimethoxycurcumin with Magnesium and Beta-Cyclodextrin

Obregón-Mendoza,

Meza-Morales,

Rodríguez-Hernández

et al. 2024

IJMS

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Breast cancer is one of the leading causes of death in the female population because of the resistance of cancer cells to many anticancer drugs used. Curcumin has cytotoxic activities against breast cancer cells, although it has limited use due to its poor bioavailability and rapid metabolic elimination. The synthesis of metal complexes of curcumin and curcuminoids is a relevant topic in the search for more active and selective derivatives of these molecular scaffolds. However, solubility and bioavailability are concomitant disadvantages of these types of molecules. To overcome such drawbacks, the preparation of inclusion complexes offers a chemical and pharmacologically safe option for improving the aqueous solubility of organic molecules. Herein, we describe the preparation of the inclusion complex of dimethoxycurcumin magnesium complex (DiMeOC-Mg, (4)) with beta-cyclodextrin (DiMeOC-Mg-BCD, (5)) in the stoichiometric relationship 1:1. This new inclusion complex’s solubility in aqueous media phosphate buffer saline (PBS) was improved by a factor of 6x over the free metal complex (4). Furthermore, 5 affects cell metabolic rate, cell morphology, cell migration, induced apoptosis, and downregulation of the matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), and signal transducer and activator of transcription-3 (STAT3) expression levels on MD Anderson metastasis breast-231 cancer (MDA-MB-231) cell lines. Results of an antitumor assay in an in ovo model showed up to 30% inhibition of tumor growth for breast cancer (MDA-MB-231) when using (5) (0.650 mg/kg dose) and 17.29% inhibition with the free homoleptic metal complex (1.5 mg/kg dose, (4)). While the formulation of inclusion complexes from metal complexes of curcuminoids demonstrates its usefulness in improving the solubility and bioavailability of these metallodrugs, the new compound (5) exhibits excellent potential for use as a therapeutic agent in the battle against breast cancer.

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Design, Preparation and Evaluation of Supramolecular Complexes with Curcumin for Enhanced Cytotoxicity in Breast Cancer Cell Lines

Cited by 4 publications

References 26 publications

Comparative Investigation into the Roles of Imipenem:Cyclodextrin Complexation and Antibiotic Combination in Combatting Antimicrobial Resistance in Gram-Negative Bacteria

Comparative Investigation into the Roles of Imipenem:Cyclodextrin Complexation and Antibiotic Combination in Combatting Antimicrobial Resistance in Gram-Negative Bacteria

Interactions of Cyclodextrins and their Hydroxyl Derivatives with Etodolac: Solubility and Dissolution Enhancement

The Antitumoral Effect In Ovo of a New Inclusion Complex from Dimethoxycurcumin with Magnesium and Beta-Cyclodextrin

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