LDH-Indomethacin Nanoparticles Antitumoral Action: A Possible Coadjuvant Drug for Cancer Therapy

Author:

Alves Kelly Costa1ORCID,Costa Carlos Emmerson Ferreira da2,Remédios Cláudio Márcio Rocha3,Calcagno Danielle Queiroz4,Lima Marcelo de Oliveira5ORCID,Silva José Rogério A.67ORCID,Alves Cláudio Nahum35ORCID

Affiliation:

1. Programa de Pós-Graduação em Ciência e Engenharia de Materiais, Universidade Federal do Pará, Belém 66075-110, Brazil

2. Programa de Pós-Graduação em Química, Universidade Federal do Pará, Belém 66075-110, Brazil

3. Instituto de Ciências Exatas e Naturais, Universidade Federal do Pará, Belém 60740-000, Brazil

4. Núcleo de Pesquisas em Oncologia, Hospital Universitário João de Barros Barreto, Universidade Federal do Pará, Belém 66075-110, Brazil

5. Programa de Pós-Graduação em Ciências e Meio Ambiente, Universidade Federal do Pará, Belém 66075-110, Brazil

6. Computer Modeling of Molecular Biosystems (CompMBio), Universidade Federal do Pará, Belém 66075-110, Brazil

7. Catalysis and Peptide Research Unit, University of KwaZulu-Natal, Durban 4041, South Africa

Abstract

Indomethacin (INDO) has a mechanism of action based on inhibiting fatty acids cyclooxygenase activity within the inflammation process. The action mechanism could be correlated with possible anticancer activity, but its high toxicity in normal tissues has made therapy difficult. By the coprecipitation method, the drug carried in a layered double hydroxides (LDH) hybrid matrix would reduce its undesired effects by promoting chemotherapeutic redirection. Therefore, different samples containing INDO intercalated in LDH were synthesized at temperatures of 50, 70, and 90 °C and synthesis times of 8, 16, 24, and 48 h, seeking the best structural organization. X-ray diffraction (XRD), vibrational Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), spectrophotometric analysis in UV-VIS, and differential thermogravimetric analysis (TGA/DTA) were used for characterization. Our results indicate that higher temperatures and longer synthesis time through coprecipitation reduce the possibility of INDO intercalation. However, it was possible to establish a time of 16 h and a temperature of 50 °C as the best conditions for intercalation. In vitro results confirmed the cell viability potential and anticancer activity in the LDH-INDO sample (16 h and 50 °C) for gastric cancer (AGP01, ACP02, and ACP03), breast cancer (MDA-MB-231 and MCF-7), melanoma (SK-MEL-19), lung fibroblast (MRC-5), and non-neoplastic gastric tissue (MN01) by MTT assay. Cell proliferation was inhibited, demonstrating higher and lower toxicity against MDA-MB-231 and SK-MEL-19. Thus, a clinical redirection of INDO is suggested as an integral and adjunctive anticancer medication in chemotherapy treatment.

Funder

CAPES/COFECUB 780/13

Publisher

MDPI AG

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