High Loading Efficiency and Controlled Release of Bioactive Immunotherapeutic Proteins Using Vaterite Nanoparticles

Nanoparticles may limit off-tumor/on-target ubiquitous activation of signaling by protein-based drugs. However, many challenges still exist in the design of a nanoparticle for protein delivery. In this study, conditions to establish vaterite nanoparticles as a pH-sensitive drug delivery system (DDS) for encapsulated protein drugs are comprehensively evaluated. Low coprecipitation pH of vaterite and protein prevents protein denaturation and yields high loading efficiency. Unprotected vaterite recrystallizes in aqueous solutions within 3 h to calcite and releases the loaded protein completely, but surface-modified particles with carboxyl groups containing polymers prove stable for more than 5 months. Notably, modification of vaterite with sulfonated polymers increases the loading of cationic proteins by a multiple. A system is developed for vaterite exposure to (pH) conditions under body-like-flow rates, with the dissolution of vaterite and simultaneous release of active proteins at tumor microenvironmental pH reaching up to 80% and only 20% at physiological pH within 2 h. Importantly, the immunomodulatory protein tumor necrosis factor preserves its native structure and fully retains functional activity in vitro after release from the particles. In conclusion, the studies described here provide a framework for the development of vaterite-based DDS as a carrier for bioactive protein-based therapeutics.     

Extended Gini-Type Measures of Risk and Variability

ABSTRACT

The aim of this paper is to introduce a risk measure, Extended Gini Shortfall (EGS), that extends the Gini-type measures of risk and variability by taking risk aversion into consideration. Our risk measure is coherent and catches variability, an important concept for risk management. The analysis is made under the Choquet integral representations framework. We expose results for analytic computation under well-known distribution functions. Furthermore, we provide a practical application.     

Valorization of Moroccan Bentonite Deposits: “Purification and Treatment of Margin by the Adsorption Process”

The main objective of this work was to contribute to the reduction in the contamination of phenolic compounds contained in margin by an adsorption process on two types of raw bentonite. The margin used in the studies was collected from a semi-modern oil mill located in the Nador–Morocco region. The results of the physico-chemical analyses showed that the effluents of the oil mills showed that they are highly polluted, particularly in terms of the total suspended solids (TSS), chemical oxygen demand (COD), and iron content of around 154.82 (mg/L), and copper content of 31.72 (mg/L). The mineralogy of bentonites studied by X-ray diffraction (XRD) reveals the existence of two types of montmorillonite; theoretically, the diffraction peak (001) of the montmorillonite appears at 15 Å, with a basal spacing that corresponds to a calcium pole, and the diffraction peak (001) appears at 12Å, with a basal spacing that corresponds to a sodium pole. The specific surface area of the bentonite used is characterized by a large specific surface area, varying between 127.62 m²·g⁻¹ and 693.04 m²·g⁻¹, which is due to the presence of hydrated interleaved cations. This surface is likely to increase in aqueous solution depending on the solid/liquid ratio that modulates the degree of hydration. With a high cation exchange capacity (CEC) (146.54 meq/100 g), samples of margin mixed with raw bentonites at different percentages vary between 5% and 100%. The potential of Moroccan bentonite for the phenol adsorption of 9.17 (g/L) from aqueous solutions was investigated. Adsorption tests have confirmed the effectiveness of these natural minerals in reducing phenolic compounds ranging from 8.72% to 76.23% contained in the margin and the efficiency of heavy metal retention through microelements on raw bentonites. The very encouraging results obtained in this work could aid in the application of adsorption for the treatment of margin.     

Synthesis and stability evaluation of novel peptidomimetic Caspase-1 inhibitors for topical application

During our search for topically-active Caspase-1 inhibitors, we identified a novel class of potent inhibitors based on a 1,3,5-trisubstituted uracil motif equipped with an l-aspartate semi-aldehyde derived warhead. In the literature, the majority of Caspase-1 inhibitors possessing the same warhead have been designed and evaluated for oral administration as the ethyl acetal pro-drug form. For our topical program, the pro-drug acetal form was not fully hydrolysed in the skin and was unstable in many of our standard topical excipients, therefore, we were obliged to focus on the actual hemiacetal drug form of the molecule during our drug discovery program. Our work focuses on both the synthesis and achiral and chiral stability of the final drug molecules in topical excipients.