Tailored Polymersomes for Enhanced Oral Drug Delivery: pH-Sensitive Systems for Intestinal Delivery of Immunosuppressants.

Ensuring precise drug release at target sites is crucial for effective treatment. Here, pH-responsive nanoparticles for oral administration of mycophenolate mofetil, an alternative therapy for patients with inflammatory bowel disease unresponsive to conventional treatments is developed. However, its oral administration presents challenges due to its low solubility in the small intestine and high solubility and absorption in the stomach. Therefore, this aim is to design a drug delivery system capable of maintaining drug solubility compared to the free drug while delaying absorption from the stomach to the intestine. Successful synthesis and assembly of a block copolymer incorporating a pH-responsive functional group is achieved. Dynamic light scattering indicated a significant change in hydrodynamic size when the pH exceeded 6.5, confirming successful incorporation of the pH-responsive group. Encapsulation and controlled release of mycophenolate mofetil are efficiently demonstrated, with 90% release observed at intestinal pH. In vitro cell culture studies confirmed biocompatibility, showing no toxicity or adverse effects on Caco-2 cells. In vivo oral rat studies indicated reduced drug absorption in the stomach and enhanced absorption in the small intestine with the developed formulation. This research presents a promising drug delivery system with potential applications in the treatment of inflammatory bowel disease.

Evaluation of the SERS performances of Tabun and VX label-free detection in complex and multicomponent fluids.

Nerve agents represent a serious threat to security worldwide. Chemical terrorism has become an alarming danger since the technological progresses have simplified the production of nerve agents. Therefore, there is an immediate demand for a fast and precise detection of these compounds on-site and real-time. In this perspective, Surface-Enhanced Raman Scattering (SERS) has emerged as a well-suited alternative for on-field detection. SERS performances of unfunctionalized SERS substrates were evaluated in realistic samples. Two nerve agents, Tabun and VX, were diluted in two matrix models: a contact lens solution, and a caffeine-based eye serum. The performance two research-grade instruments and two portable devices were compared. Despite the use of a small sampling volume of complex matrices without any sample pre-treatment, we achieved Tabun detection in both media, with a practical limit of detection (LOD) in the range of 7-9 ppm in contact lens liquid, and of 10.2 ppm in eye serum. VX detection turned out to be more challenging and was achieved only in contact lens solution, with a practical LOD in the range of 0.6-5 ppm. These results demonstrate the feasibility of on-field detection of nerve agents with SERS, that could be implemented when there is suspicion of chemical threat.

Label-free SERS assay combined with multivariate spectral data analysis for lamotrigine quantification in human serum.

Considering the need for a more time and cost-effective method for lamotrigine (LTG) detection in clinics we developed a fast and robust label-free assay based on surface-enhanced Raman scattering (SERS) for LTG quantification from human serum. The optimization and application of the developed assay is presented  showing the: (i) exploration of different methods for LTG separation from human serum; (ii) implementation of a molecular adsorption step on an ordered Au nanopillar SERS substrate; (iii) adaptation of a fast scanning of the SERS substrate, performed with a custom-built compact Raman spectrometer; and (iv) development of LTG quantification methods with univariate and multivariate spectral data analysis. Our results showed, for the first time, the SERS-based characterization of LTG and its label-free identification in human serum. We found that combining a miniaturized solid phase extraction, as sample pre-treatment with the SERS assay, and using a multivariate model is an optimal strategy for LTG quantification in human serum in a linear range from 9.5 to 75 µM, with LoD and LoQ of 3.2 µM and 9.5 µM, respectively, covering the suggested clinical therapeutic window. We also showed that the developed assay allowed for quantifying LTG from human serum in the presence of other drugs, thereby demonstrating the robustness of label-free SERS. The sensing approach and instrumentation can be further automated and integrated in devices that can advance the drug monitoring in real clinical settings.

Polyester fabric-based nano copper-polyhedral oligomeric silsesquioxanes sorbent for thin film extraction of non-steroidal anti-inflammatory drugs.

In this study, in-situ preparation of copper nanoparticles under sonoheating conditions followed by coating on commercial polyester fabric is reported. Through the self-assembly interaction of thiol groups and copper nanoparticles, the modified polyhedral oligomeric silsesquioxanes (POSS) was deposited on the fabric's surface. In the next step, radical thiol-ene click reactions were implemented to create more layers of POSSs. Subsequently, the modified fabric was applied for sorptive thin film extraction of non-steroidal anti-inflammatory drugs (NSAIDs) including naproxen, ibuprofen, diclofenac, and mefenamic acid from urine samples, followed by high-performance liquid chromatography equipped with a UV detector. The morphology of the prepared fabric phase was characterized by scanning electron microscopy, water angle contact, energy dispersive spectrometry mapping, analysis of nitrogen adsorption-desorption isotherms, and attenuated total reflectance Fourier transform infrared spectroscopy. The significant extraction parameters, including the acidity of the sample solution, desorption solvent and its volume, extraction time, and desorption time, were investigated using the one-variable-at-a-time approach. Under the optimal condition, NSAIDs' detection limit was 0.3-1 ng mL-1 with a wide linear range of 1-1000 ng mL-1. The recovery values were between 94.0% and 110.0%, with relative standard deviations of less than 6.3%. The prepared fabric phase exhibited acceptable repeatability, stability, and sorption property toward NSAIDs in urine samples.

Perylene bisimide-based nanocubes for selective vapour phase ultra-trace detection of aniline derivatives.

Rapid and selective detection of biomarkers at trace levels is a highly coveted objective in the early diagnosis of cancer. Herein, we disclose the design and synthesis of a polyhedral oligomeric silsesquioxane (POSS) substituted perylene diimide. This compound is fully characterized in solution by multi nuclear NMR, as well as in gas state by ESI-MS. Surprisingly, solid-state characterization revealed an unusual cubic morphology with particle dimensions of 80-160 nm. Fluorescence studies indicate that the bulky POSS units effectively prevent perylene's aggregation caused quenching, yielding quantum yields as high as 92%. Exposing the sensor droplet-cast on quartz to anline and o-toluidine, two important biomarkers for lung cancer, results in very highly reproducible, reversible and selective fluorescence quenching responses, with LODs as low as 19 and 8 ng L-1, and linear ranges of 65-350 and 25-450 ng L-1 respectively. Mechanistic investigations point to photoinduced electron transfer (PET) as the operative pathway responsible for fluorescence quenching.

Perylene diimide-POSS network for semi selective solid-phase microextraction of lung cancer biomarkers in exhaled breath.

Lung cancer (LC) is the leading cause of cancer mortality so, the analysis of exhaled human breath has great significance for early non-invasive diagnosis. Poor selectivity and strong humidity are two bottlenecks for the application of gas sensors to exhaled breath analysis. The development of novel extractive phases for the analysis of exhaled breath by chromatography is therefore a lucrative object. Polyhedral oligomeric silsesquioxanes (POSS) are among the 3D porous materials whose unique properties make them promising coatings for solid-phase microextraction (SPME). Selective enrichment of polar or nonpolar targets depends on the pore size and functional groups on the POSSs. Herein, we disclosed 3D network of POSS-naphthalene diimide (POSS-NDI) and perylene diimide (POSS-PDI) as extractive phases for analysis of lung cancer biomarkers with the capability of capturing different volatile organic compounds (VOCs). The synthesized diimides were fully characterized by FT-IR, multinuclear NMR, SEM, TEM, TGA, and BET analysis. After optimization of all the influential parameters on sorption/desorption, figures of merit for three aldehydes as biomarkers of LC were obtained. The exhaled breath of twelve participants including seven healthy candidates and five cases with LC were examined. The partial least squares-discriminant analysis (PLS-DA) was implemented which led to the proper classification of healthy and LC patients with R2 calibration and cross-validation of 0.9738 and o.7882, respectively.