7 research outputs found
Synthesis and Validation of a Bioinspired Catechol-Functionalized Pt(IV) Prodrug for Preclinical Intranasal Glioblastoma Treatment
Simple Summary Glioblastoma (GB) is a type of brain cancer with a poor prognosis and few improvements in its treatment. One of the greatest difficulties in GB therapy lies in the fact that most of the drugs with high anticancer potential do not reach the brain and exert high therapeutic activity while minimizing side effects. To overcome these limitations, we focused on a catechol-based Pt(IV) prodrug (able to reverse cisplatin in a cellular environment) with the intention of repurposing Pt-based drugs as GB chemotherapeutic agents. Our in vitro results have corroborated the therapeutic effect of the synthesized complexes as comparable to cisplatin, and in vivo studies have demonstrated the potential of nose-to-brain delivery of this Pt(IV) prodrug for GB treatment. Glioblastoma is the most malignant and frequently occurring type of brain tumors in adults. Its treatment has been greatly hampered by the difficulty to achieve effective therapeutic concentration in the tumor sites due to its location and the blood-brain barrier. Intranasal administration has emerged as an alternative for drug delivery into the brain though mucopenetration, and rapid mucociliary clearance still remains an issue to be solved before its implementation. To address these issues, based on the intriguing properties of proteins secreted by mussels, polyphenol and catechol functionalization has already been used to promote mucopenetration, intranasal delivery and transport across the blood-brain barrier. Thus, herein we report the synthesis and study of complex 1, a Pt(IV) prodrug functionalized with catecholic moieties. This complex considerably augmented solubility in contrast to cisplatin and showed a comparable cytotoxic effect on cisplatin in HeLa, 1Br3G and GL261 cells. Furthermore, preclinical in vivo therapy using the intranasal administration route suggested that it can reach the brain and inhibit the growth of orthotopic GL261 glioblastoma. These results open new opportunities for catechol-bearing anticancer prodrugs in the treatment for brain tumors via intranasal administration
Multiproject–multicenter evaluation of automatic brain tumor classification by magnetic resonance spectroscopy
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Optimization and dust emissions analysis of the air jigging technology applied to the recycling of construction and demolition waste
© 2020. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/This work aims to evaluate the use of the air jigging technique, a density-based separation technology commonly
applied in mineral processing, to upgrade the quality of mixtures (density and geometric properties) that represents
the typical composition of construction and demolition waste (CDW) produced in Brazil. In this sense,
tests involving the variation of the main operational parameters of jigging (bed expansion rate, pulsation frequency
and jigging time) were carried out aiming to find those which provided the best recycled aggregates
quality after processing. Also, fines and dust emissions generation during jigging were measured in order to
estimate their potential impacts on human health and environment. The results showed that the air jigging
process is adequate to improve the quality of CDW by increasing the concrete concentration in the dense product.
The use of high bed expansion rates showed to be of major importance to decrease the content of ceramic aggregates in the dense product, allowing obtaining products richer in concrete. Also, the measured properties of
the obtained aggregates (size distribution, shape, etc) met the usual standards required for natural aggregates.
Finally, material losses and dust emissions generated were negligible in comparison to the total mass processed,
although special attention must be given to safety measures due the presence of inhalable particles (<10 µm).Peer ReviewedPostprint (author's final draft