Overcoming environmental problems of biocides: Synthetic bile acid derivatives as a sustainable alternative.

Marine biofouling represents a global economic and ecological challenge. Some marine organisms produce bioactive metabolites, such as steroids, that inhibit the settlement and growth of fouling organisms. The aim of this work was to explore bile acids as a new scaffold with antifouling (AF) activity by using chemical synthesis to produce a series of bile acid derivatives with optimized AF performance and understand their structure-activity relationships. Seven bile acid derivatives were successfully synthesized in moderate to high yields, and their structures were elucidated through spectroscopic methods. Their AF activities were tested against both macro- and microfouling communities. The most potent bile acid against the settlement of Mytilus galloprovincialis larvae was the methyl ester derivative of cholic acid (10), which showed an EC50 of 3.7 µM and an LC50/EC50 > 50 (LC50 > 200 µM) in AF effectiveness vs toxicity studies. Two derivatives of deoxycholic acid (5 and 7) potently inhibited the growth of biofilm-forming marine bacteria with EC50 values < 10 µM, and five bile acids (1, 5, and 7-9) potently inhibited the growth of diatoms, showing EC50 values between 3 and 10 µM. Promising AF profiles were achieved with some of the synthesized bile acids by combining antimacrofouling and antimicrofouling activities. Initial studies on the incorporation of one of these promising bile acid derivatives in polymeric coatings, such as a marine paint, demonstrated the ability of these compounds to generate coatings with antimacrofouling activity.

Transdermal delivery of a somatostatin receptor type 2 antagonist using microneedle patch technology for hypoglycemia prevention.

Hypoglycemia is a serious and potentially fatal complication experienced by people with insulin-dependent diabetes. The complication is usually caused by insulin overdose, skipping meals, and/or excessive physical activities. In type 1 diabetes (T1D), on top of impaired pancreatic α-cells, excessive levels of somatostatin from δ-cells further inhibit glucagon secretion to counteract overdosed insulin. Herein, we aimed to develop a microneedle (MN) patch for transdermal delivery of a peptide (PRL-2903) that antagonizes somatostatin receptor type 2 (SSTR2) in α-cells. First, we investigated the efficacy of subcutaneously administered PRL-2903 and identified the optimal dose (i.e., the minimum effective dose) and treatment scheduling (i.e., the best administration time for hypoglycemia prevention) in a T1D rat model. We then designed an MN patch using a hyaluronic acid (HA)-based polymer. The possible effect of the polymer on stabilizing the native structure of PRL-2903 was studied by molecular dynamics (MD) simulations. The results showed that the HA-based polymer could stabilize the PRL-2903 structure by restricting water molecules, promoting intra-molecular H-bonding, and constraining torsional angles of important bonds. In vivo studies with an overdose insulin challenge revealed that the PRL-2903-loaded MN patch effectively increased the plasma glucagon level, restored the counter-regulation of blood glucose concentration, and prevented hypoglycemia. The proposed MN patch is the first demonstration of a transdermal microneedle patch designed to deliver an SSTR2 antagonist for the prevention of hypoglycemia. This counter-regulatory peptide delivery system may be applied alongside with insulin delivery systems to provide a more effective and safer treatment for people with insulin-dependent diabetes.

Monitoring of the cellulosic ethanol fermentation process by near-infrared spectroscopy.

Rapid, efficient, and low-cost technologies for monitoring the fermentation process during second generation (2G) or cellulosic ethanol production are essential for the successful implementation of this process at the commercial scale. Here, the use of near-infrared (NIR) spectroscopy associated with partial least squares (PLS) regression was investigated as a tool for monitoring the production of 2G ethanol from lignocellulosic sugarcane residues including bagasse, straw, and tops. The spectral data was based on a set of 103 alcoholic fermentation samples. Models based on different pre-processing techniques were evaluated. The best root mean square error of prediction (RMSEP) values obtained in the external validation were around 3.02 g/L for ethanol and 6.60 g/L for glucose. The findings showed that the PLS-NIR methodology was efficient in accurately predicting the glucose and ethanol concentrations during the production of 2G ethanol, demonstrating potential for use in monitoring and control of large-scale industrial processes.