Search

There is a serious need of pediatric drug formulations, whose lack causes the frequent use of extemporaneous preparations obtained from adult dosage forms, with consequent safety and quality risks. Oral solutions are the best choice for pediatric patients, due to administration ease and dosage-adaptability, but their development is challenging, particularly for poorly soluble drugs. In this work, chitosan nanoparticles (CSNPs) and nanostructured lipid carriers (NLCs) were developed and evaluated as potential nanocarriers for preparing oral pediatric solutions of cefixime (poorly soluble model drug). The selected CSNPs and NLCs showed a size around 390 nm, Zeta-potential > 30 mV, and comparable entrapment efficiency (31–36%), but CSNPs had higher loading efficiency (5.2 vs. 1.4%). CSNPs maintained an almost unchanged size, homogeneity, and Zeta-potential during storage, while NLCs exhibited a marked progressive Zeta-potential decrease. Drug release from CSNPs formulations (differently from NLCs) was poorly affected by gastric pH variations, and gave rise to a more reproducible and controlled profile. This was related to their behavior in simulated gastric conditions, where CSNPs were stable, while NLCs suffered a rapid size increase, up to micrometric dimensions. Cytotoxicity studies confirmed CSNPs as the best nanocarrier, proving their complete biocompatibility, while NLCs formulations needed 1:1 dilution to obtain acceptable cell viability values. [ABSTRACT FROM AUTHOR]

Abstract: A series of novel spiropyrazoline oxindole derivatives was synthesized by 1,3-dipolar cycloaddition reaction. The compounds were screened for their in vitro cytotoxic activity against MCF-7 breast cancer cell line (estrogen receptor positive (ER+) and human epidermal growth factor receptor 2 negative (HER2−)). Of the nineteen spiropyrazoline oxindoles tested, six compounds have a GI50 below 12 μM The most potent compounds in this series were also evaluated against MDA-MB-231 breast cancer cell line (ER− and HER2−). Two spiropyrazoline oxindoles were highly selective between MCF-7 tumor cells and MDA-MB-231 tumor cells. More importantly, they were noncytotoxic against HEK 293T non tumor derived cell lines. [Copyright &y& Elsevier]

Several metallic nanomaterials (NMs), such as titanium dioxide nanomaterials (TiO2), present beneficial properties with a broad range of innovative applications. The human population is exposed to TiO2, particularly by ingestion, due to its increasing use as a food additive and inclusion in dietary supplements and food packaging materials. Whether this oral exposure may lead to adverse local or systemic outcomes has been the subject of research, but studies have generated contradictory results, reflecting differences in the physicochemical properties of the TiO2 studied, effects of the surrounding matrix, and modifications during digestion. This work aimed to investigate the toxic effects of three different TiO2 NMs (NM-103, NM-103 and NM-105) on the gastrointestinal tract cells, Caco-2 and HT29-MTX-E12, after the use of the standardized static INFOGEST 2.0 in vitro digestion method to mimic human digestion of TiO2, contributing to hazard assessment. The results show that, for one of the digested TiO2 NMs studied (NM-105), a more pronounced toxicity occurs after exposure of HT29-MTX-E12 intestinal cells, as compared to undigested NM, concomitantly with subtle changes in characteristics of the NM. Thus, the inclusion of the digestion simulation in the safety evaluation of ingested NMs through in vitro bioassays can better integrate the modifications that NMs suffer in the organism. It is expected that such an approach will reduce uncertainties in the hazard assessment of ingested NMs for human health. [ABSTRACT FROM AUTHOR]

Gastric cancer is one of the deadliest cancers in modern societies, so there is a high level of interest in discovering new drugs for this malignancy. Previously, we demonstrated the ability of tryptophanol-derived polycyclic compounds to activate the tumor suppressor protein p53, a relevant therapeutic target in cancer. In this work, we developed a novel series of enantiomerically pure tryptophanol-derived small molecules to target human gastric adenocarcinoma (AGS) cells. From an initial screening of fourteen compounds in AGS cell line, a hit compound was selected for optimization, leading to two derivatives selective for AGS gastric cells over other types of cancer cells (MDA-MB-231, A-549, DU-145, and MG-63). More importantly, the compounds were non-toxic in normal cells (HEK 293T). Additionally, we show that the growth inhibition of AGS cells induced by these compounds is mediated by apoptosis. Stability studies in human plasma and human liver microsomes indicate that the compounds are stable, and that the major metabolic transformations of these molecules are mono- and di-hydroxylation of the indole ring. [ABSTRACT FROM AUTHOR]

The design and synthesis of a library of twenty-six spirotriazoline oxindoles and their in vitro evaluation as potential anticancer agents is reported. The antiproliferative activity of the synthesized compounds was assessed against four different cancer cell lines (HCT-116 p53 (+/+) , HCT-116 p53 (−/−) , MCF-7, and MDA-MB-231). Four spirotriazoline oxindoles showed selectivity against the four cancer cell lines tested over the non-cancer derived HEK 293T cell line. To characterize the molecular mechanisms involved in compound antitumoral activity, two spirotriazoline oxindoles were selected for further studies. Both compounds were able to induce apoptosis and cell cycle arrest at G0/G1 phase and upregulated p53 steady-state levels, while decreasing its main inhibitor MDM2, in HCT-116 cells. Importantly, cytotoxic effects induced by spirotriazoline oxindoles occurred in cancer cells without eliciting cell death in non-malignant CCD-18Co human colon fibroblasts. In addition, four spirotriazoline oxindoles showed selectivity against the triple-negative breast cancer cell line MDA-MB-231 with IC 50 values of 3.5–6.7 μM. These results highlight the anticancer potential of spirotriazoline oxindoles, especially when dealing with aggressive and challenging triple-negative breast cancer. [ABSTRACT FROM AUTHOR]