Development and In Vitro and In Vivo Evaluation of an Antineoplastic Copper(II) Compound (Casiopeina III-ia) Loaded in Nonionic Vesicles Using Quality by Design

Aguilar-Jiménez, Zenayda; González-Ballesteros, Mauricio; Dávila-Manzanilla, Silvia Graciela; Espinoza-Guillén, Adrián; Ruíz-Azuara, Lena

doi:10.3390/ijms232112756

Cited by 11 publications

(5 citation statements)

References 67 publications

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“…The ATR-FTIR analysis revealed the structural properties of our niosomes and their interaction with the niosomal components. Notably, the absence of characteristic peaks for CXB in its niosomal formulations and the minor shifts observed for MET niosomes, as described earlier, indicate effective encapsulation of the drug within the niosomal core rather than the surface as reported, respectively, by Aguilar-Jiménez et al and Alkilani et al [10,51].…”

Section: Discussionsupporting

confidence: 70%

Niosomal Delivery of Celecoxib and Metformin for Targeted Breast Cancer Treatment

Basheer,

Alhusban,

Zaid Alkilani

et al. 2023

Cancers

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Breast cancer continues to be a prominent worldwide health concern and requires continued investigation into innovative therapeutic approaches. Here, we report the first investigation into the therapeutic efficacy of combining Metformin (MET) and Celecoxib (CXB), both in free and niosomal form, for the treatment of breast cancer. Our investigation encompassed the characterization of these niosomal drug carriers, their stability assessment, and their effect on breast cancer cell models. The thin-film hydration technique was employed to prepare niosomes with spherical, uniform-size distributions and high encapsulation efficiencies. The niosomes were characterized by TEM, particle size analyzer, and ATR-FTIR. The niosomes with an average size of 110.6 ± 0.6 and 96.7 ± 0.7, respectively, for MET and CXB were stable when stored at 4 °C for three months with minimal drug leakage, minor changes in encapsulation efficiency and size, and unchanged physicochemical parameters. Evaluation in two-dimensional (2D) and three-dimensional (3D) viability assays demonstrated an increased cytotoxicity of encapsulated drugs when compared to their free-drug counterparts. Additionally, the combination of Metformin Niosomal Particles (MET NPs) and Celecoxib Niosomal Particles (CXB NPs) led to decreased cell viability in both 2D and 3D models compared to each drug administered individually. When comparing the effect of the niosomal versus the free combination of the drugs on cell migration, we found that both interventions effectively prevented cell migration. However, the efficacy of the niosomes’ combination was not superior to that of the free drug combination (p < 0.05). In conclusion, the results of this study provide valuable insights into the potential application of combining MET and CXB nanoparticle delivery systems to breast cancer treatment. Exploring the in vivo application of this drug delivery system could open new avenues for more effective and targeted therapeutic approaches for breast cancer patients.

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Section: Discussionsupporting

confidence: 70%

Niosomal Delivery of Celecoxib and Metformin for Targeted Breast Cancer Treatment

Basheer,

Alhusban,

Zaid Alkilani

et al. 2023

Cancers

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“…This potential of copper complexes to produce antitumor compounds has led to the development of several copper complexes that present antitumor activity, even when the ligands are biologically inactive [ 3 ]. The compounds in the family Casiopeinas ® are among the most studied copper complexes, with Casiopeina III-ia, [(Cu(II))(4,4′-dimethyl-2,2′-bipyridine)(acetylacetonate)(NO 3 )(H 2 O)], being tested in a clinical phase I trial in Mexico [ 7 , 8 ]. Another relevant compound is HydroCuP ® , [Cu(tris-hydroxymethylphosphino) 4 ][PF 6 ], which is highly selective towards cancer cells and has presented promising results in advanced preclinical studies [ 9 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

New Copper(II)-L-Dipeptide-Bathophenanthroline Complexes as Potential Anticancer Agents—Synthesis, Characterization and Cytotoxicity Studies—And Comparative DNA-Binding Study of Related Phen Complexes

et al. 2023

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Searching for new copper compounds which may be useful as antitumor drugs, a series of new [Cu(L-dipeptide)(batho)] (batho:4,7-diphenyl-1,10-phenanthroline, L-dipeptide: Gly-Val, Gly-Phe, Ala-Gly, Ala-Ala, Ala-Phe, Phe-Ala, Phe-Val and Phe-Phe) complexes were synthesized and characterized. To interpret the experimental IR spectra, [Cu(ala-gly)(batho)] was modelled in the gas phase using DFT at the B3LYP/LANL2DZ level of theory and the calculated vibrational frequencies were analyzed. Solid-state characterization is in agreement with pentacoordinate complexes of the general formula [Cu(L-dipeptide)(batho)]·x solvent, similar to other [Cu(L-dipeptide)(diimine)] complexes. In solution, the major species are heteroleptic, as in the solid state. The mode of binding to the DNA was evaluated by different techniques, to understand the role of the diimine and the dipeptide. To this end, studies were also performed with complexes [CuCl2(diimine)], [Cu(L-dipeptide)(diimine)] and free diimines, with phenanthroline, neocuproine and 3,4,7,8-tetramethyl-phenanthroline. The cytotoxicity of the complexes was determined on human cancer cell lines MDA-MB-231, MCF-7 (breast, the first triple negative), and A549 (lung epithelial) and non-tumor cell lines MRC-5 (lung) and MCF-10A (breast). [Cu(L-dipeptide)(batho)] complexes are highly cytotoxic as compared to cisplatin and [Cu(L-dipeptide)(phenanthroline)] complexes, being potential candidates to study their in vivo activity in the treatments of aggressive tumors for which there is no curative pharmacological treatment.

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“…It was observed that encapsulated CasIIIia showed lower toxicity in female BALB/c mice with cells 4t1 (metastatic breast cancer model), compared with cis-Pt and nonencapsulated CasIIIia. When the weight of mice was evaluated at the end of the treatment, it was observed that only the groups treated with niosome with CasIIIia and niosome without CasIIIia recovered their initial weights [126]. Also, a Cu(II) complex containing a b-diketone and phenanthroline has been synthesized, and the nanoparticles of this complex were prepared and evaluated in for their effects on the proliferation of MKN-45 cells.…”

Section: Encapsulationmentioning

confidence: 99%

The Importance of Being Casiopeina as Polypharmacologycal Profile (Mixed Chelate–Copper (II) Complexes and Their In Vitro and In Vivo Activities)

Aguilar-Jiménez,

Espinoza-Guillén,

Resendiz-Acevedo

et al. 2023

Inorganics

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In this review, we present a timeline that shows the origin of mixed chelate copper (II) complexes, registered as Mark Title Casiopeínas®, as the first copper (II) compounds proposed as anticancer drugs in 1988 and 1992. In the late twentieth century, the use of essential metals as anticancer agents was not even considered, except for their antifungal or antibacterial effects; also, copper, as gold salts, was used for arthritis problems. The use of essential metals as anticancer drugs to diminish the secondary toxic effects of Cisplatin was our driving force: to find less toxic and even more economical compounds under the rational design of metal chelate complexes. Due to their chemical properties, copper compounds were the choice to continue anticancer drug development. In this order of ideas, the rational designs of mixed chelate–copper (II) complexes (Casiopeínas, (Cas) homoleptic or heteroleptic, depending on the nature of the secondary ligand) were synthesized and fully characterized. In the search for new, more effective, and less toxic drugs, Casiopeína® (Cas) emerged as a family of approximately 100 compounds synthesized from coordinated Cu(II) complexes with proven antineoplastic potential through cytotoxic action. The Cas have the general formula [Cu(N–N)(N–O)]NO3 and [Cu(N–N)(O–O)]NO3, where N–N is an aromatic substituted diimine (1,10-phenanthroline or 2,2′-bipyridine), and the oxygen donor (O–O) is acetylacetonate or salicylaldehyde. Lately, some similar compounds have been developed by other research groups considering a similar hypothesis after Casiopeína’s discoveries had been published, as described herein. As an example of translational medicine criteria, we have covered each step of the established normative process for drug development, and consequently, one of the molecules (Casiopeína III ia (CasIIIia)) has reached the clinical phase I. For these copper compounds, other activities, such as antibacterial, antiparasitic and antiviral, have been discovered.

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Development and In Vitro and In Vivo Evaluation of an Antineoplastic Copper(II) Compound (Casiopeina III-ia) Loaded in Nonionic Vesicles Using Quality by Design

Cited by 11 publications

References 67 publications

Niosomal Delivery of Celecoxib and Metformin for Targeted Breast Cancer Treatment

Niosomal Delivery of Celecoxib and Metformin for Targeted Breast Cancer Treatment

New Copper(II)-L-Dipeptide-Bathophenanthroline Complexes as Potential Anticancer Agents—Synthesis, Characterization and Cytotoxicity Studies—And Comparative DNA-Binding Study of Related Phen Complexes

The Importance of Being Casiopeina as Polypharmacologycal Profile (Mixed Chelate–Copper (II) Complexes and Their In Vitro and In Vivo Activities)

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