Assessing the impact of antineoplastic drugs in the aquatic environment: State of the art and future perspective for freshwater organisms

Damasceno, Évila Pinheiro; Ribeiro, Fabianne; Costa-Lotufo, L. V.; Soares, Amadeu M.V.M.; Pavlaki, Maria D.; Loureiro, Susana

doi:10.1016/j.etap.2023.104109

Cited by 6 publications

(3 citation statements)

References 66 publications

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“…Higher ecotoxicity was observed for 5-fluorouracil (EC 50 = 0.027 mg L −1 ) and cisplatin (EC 50 = 1.20 mg L −1 ), while lower ecotoxicity was noticed for cyclophosphamide, doxorubicin, and etoposide. The difference in the ecotoxicity of bleomycin and vincristine to Pseudomonas putida after 16 h was noticed; EC 50 for bleomycin was 7.27 mg L −1 , while vincristine did not cause significant effects on bacterial growth up to 100 mg L −1 [ 61 ]. Furthermore, Pseudomonas putida is a bacterium that has a rich enzymatic composition and is therefore frequently used for bioremediation purposes [ 62 ].…”

Section: Resultsmentioning

confidence: 99%

Polymeric Amorphous Solid Dispersions of Dasatinib: Formulation and Ecotoxicological Assessment

Sokač,

Miloloža,

Kučić Grgić

et al. 2024

Pharmaceutics

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Dasatinib (DAS), a potent anticancer drug, has been subjected to formulation enhancements due to challenges such as significant first-pass metabolism, poor absorption, and limited oral bioavailability. To improve its release profile, DAS was embedded in a matrix of the hydrophilic polymer polyvinylpyrrolidone (PVP). Drug amorphization was induced in a planetary ball mill by solvent-free co-grinding, facilitating mechanochemical activation. This process resulted in the formation of amorphous solid dispersions (ASDs). The ASD capsules exhibited a notable enhancement in the release rate of DAS compared to capsules containing the initial drug. Given that anticancer drugs often undergo limited metabolism in the body with unchanged excretion, the ecotoxicological effect of the native form of DAS was investigated as well, considering its potential accumulation in the environment. The highest ecotoxicological effect was observed on the bacteria Vibrio fischeri, while other test organisms (bacteria Pseudomonas putida, microalgae Chlorella sp., and duckweed Lemna minor) exhibited negligible effects. The enhanced drug release not only contributes to improved oral absorption but also has the potential to reduce the proportion of DAS that enters the environment through human excretion. This comprehensive approach highlights the significance of integrating advances in drug development while considering its environmental implications.

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Section: Resultsmentioning

confidence: 99%

Polymeric Amorphous Solid Dispersions of Dasatinib: Formulation and Ecotoxicological Assessment

Sokač,

Miloloža,

Kučić Grgić

et al. 2024

Pharmaceutics

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“…Zebrafish embryos are a useful, predictive, and well-established model to assess the toxicity displayed by nano-complexes since, as the genomes of these animals and humans are closely related, results can predict potential effects on humans [ 73 , 74 ]. Furthermore, this model is easy to manipulate and economical compared to other animal models [ 74 , 75 , 76 ]. Since several adults can be maintained in small-scale aquariums, this model system provides several hundreds of eggs in one breeding event.…”

Section: Resultsmentioning

confidence: 99%

“…Since several adults can be maintained in small-scale aquariums, this model system provides several hundreds of eggs in one breeding event. The optical transparency of embryos allows easy visualization of organ morphology and possible malformations, thus avoiding invasive techniques [ 74 , 75 , 76 ]. Some recent studies have highlighted the importance of this kind of model to test nanoparticle toxicity [ 73 , 77 , 78 , 79 , 80 , 81 ].…”

Section: Resultsmentioning

confidence: 99%

Evidence That a Peptide-Drug/p53 Gene Complex Promotes Cognate Gene Expression and Inhibits the Viability of Glioblastoma Cells

Neves,

Albuquerque,

Faria

et al. 2024

Pharmaceutics

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Glioblastoma multiform (GBM) is considered the deadliest brain cancer. Conventional therapies are followed by poor patient survival outcomes, so novel and more efficacious therapeutic strategies are imperative to tackle this scourge. Gene therapy has emerged as an exciting and innovative tool in cancer therapy. Its combination with chemotherapy has significantly improved therapeutic outcomes. In line with this, our team has developed temozolomide–transferrin (Tf) peptide (WRAP5)/p53 gene nanometric complexes that were revealed to be biocompatible with non-cancerous cells and in a zebrafish model and were able to efficiently target and internalize into SNB19 and U373 glioma cell lines. The transfection of these cells, mediated by the formulated peptide-drug/gene complexes, resulted in p53 expression. The combined action of the anticancer drug with p53 supplementation in cancer cells enhances cytotoxicity, which was correlated to apoptosis activation through quantification of caspase-3 activity. In addition, increased caspase-9 levels revealed that the intrinsic or mitochondrial pathway of apoptosis was implicated. This assumption was further evidenced by the presence, in glioma cells, of Bax protein overexpression—a core regulator of this apoptotic pathway. Our findings demonstrated the great potential of peptide TMZ/p53 co-delivery complexes for cellular transfection, p53 expression, and apoptosis induction, holding promising therapeutic value toward glioblastoma.

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Pharmaceuticals contamination in the environment

Ghazal

2023

Environmental Toxicology and Pharmacology

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Assessing the impact of antineoplastic drugs in the aquatic environment: State of the art and future perspective for freshwater organisms

Cited by 6 publications

References 66 publications

Polymeric Amorphous Solid Dispersions of Dasatinib: Formulation and Ecotoxicological Assessment

Polymeric Amorphous Solid Dispersions of Dasatinib: Formulation and Ecotoxicological Assessment

Evidence That a Peptide-Drug/p53 Gene Complex Promotes Cognate Gene Expression and Inhibits the Viability of Glioblastoma Cells

Pharmaceuticals contamination in the environment

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