L-Asparaginase delivery systems targeted to minimize its side-effects.

L-asparaginase (L-ASP) is one of the key enzymes used in therapeutic applications, particularly to treat Acute Lymphocytic Leukemia (ALL). L-asparagine is a non-essential amino acid, which means that it can be synthesized by the body and is not required to be obtained through the diet. The synthesis of L-asparagine occurs primarily in the liver, but it also takes place in other tissues throughout the body. In contrast, leukemic cells cannot synthesize L-asparagine due the absence of L-asparagine synthetase and should obtain it from circulating sources for protein synthesis and cell division processes to ensure their vital functions. L-ASP catalyzes the deamination process of L-asparagine amino-acid into aspartic acid and ammonia, depriving leukemic cells of asparagine. This leads to decreased protein synthesis and cell division in tumor cells. However, using L-ASP has side effects, such as hypersensitivity or allergic reaction, antigenicity, short half-life, temporary blood clearance, and toxicity. L-ASP immobilization can minimize the side effects of L-ASP by stopping the immune system from attacking non-human enzymes and improving the enzyme's performance. The first strategy includes modification of enzyme structure, such as covalent binding (conjugation), adsorption to the support material and cross-linking of the enzyme. The chemical modification of residues, often nonspecific, changes the enzyme's hydrophobicity and surface charge, lowering the enzyme's activity. Also, the first strategy exposes the enzyme's surface to the environment. This eliminates its performance and does not allow targeted delivery of the enzyme. The second strategy is based on the entrapment of the enzyme inside the protecting structure or encapsulation. This strategy offers the same benefits as the first. Still, it also enables reducing toxicity, prolonging in vivo half-life, enhancing stability and activity, enables a targeted delivery and controlled release of the enzyme. Compared to the first strategy, encapsulation does not modify the chemical structure of the enzyme since L-ASP is only effective against leukemia in its native tetrameric form. This review aims to present state of the art in L-ASP formulations developed for reducing the side effects of L-ASP, focusing on describing improvements in their safety. The primary focus in the field remains to be improving the overall performance of the L-ASP formulations. Almost all encapsulation systems allow reducing immune response due to screening the enzyme from antibodies and prolonging its half-life. However, the enzyme's activity and stability depend on the encapsulation system type. Therefore, the selection of the right encapsulation system is crucial in therapy due to its effect on the performance parameters of the L-ASP. Biodegradable and biocompatible materials, such as chitosan, alginate and liposomes, mainly attract the researcher's interest in enzyme encapsulation. The research trends are also moving towards developing formulations with targeted delivery and increased selectivity.

Temperature-Responsive Pyraclostrobin-Loaded Octadecane Submicrocapsules with Lowered Toxicity.

Pyraclostrobin (Pyr) is one of the most effective fungicides. However, it can degrade via photolysis in water, it is toxic to aquatic life and if inhaled, it has a low solubility in water, that leads to difficulties when applying to plants by spraying. Additionally, the necessity of repeated (weekly) sprays of fungicides when the pathogen growth risk is the highest, such as at the temperature range of 24 to 36 °C and increased humidity of about 95%, leads to loss of efficiency of the fungicide and overdose of chemicals. In the present study, pyraclostrobin was microencapsulated to solve the abovementioned issues. As a core of capsules octadecane (OD) with a melting point of 28 °C was used, thus, the release of pyraclostrobin was controlled via temperature change. Pyraclostrobin-loaded submicrocapsules (PyrSMCs) were characterized using SEM, DLS, TGA/DSC, HPLC, FTIR methods; stimuli-responsivity was tested employing in vitro tests with pathogenic culture (Fungal strain of Pyrenophora teres - CPPF-453) grown in Petri dishes. Toxicity of PyrSMCs to Artemia salina was studied as well. Size of capsules was 200-600 nm along with the presence of bigger capsules with a diameter of 1-4 µm. PyrSMCs showed excellent antifungal effects above the melting point of octadecane. PyrSMCs demonstrated 29 times less toxicity than pyraclostrobin of technical grade. Overall, results show the potential of such capsules to be applied in the agricultural industry for precise agriculture strategies.

Recent advances and remaining barriers to producing novel formulations of fungicides for safe and sustainable agriculture.

BACKGROUND: Fungi have evolved for 1 billion years and due to their adaptability and resilience can be found in multiple habitats around the globe. Among numerous species of fungi, some are pathogenic, and humans have battled since the dawn of organized agriculture to reduce production losses. With the arrival of fungicides many gains have been made in this struggle. However, though fungicides have greatly contributed to substantial increase in agricultural productivity, their over usage has led to both health and environmental repercussions. They remain cornerstone of the agriculture industry, however, development of safer formulations to champion sustainable and eco-friendly agriculture is of great importance, especially in face of a growing global population, climate change and increasing fungal resistance to existing compounds. SCOPE AND APPROACH: The aim of this review is to present the state of the art in fungicides formulations developed for agrochemistry, also describing recent improvements in their safety, with special focus on fungicides used most against the ten most important fungal pathogens. KEY FINDINGS AND CONCLUSIONS: The major focus in the field remains to be the improvement of the overall performance of the fungicide formulations. The research trends are also moving towards developing more eco-friendly formulations. However, there are still very few studies assessing nanoformulations toxicity and environmental impact. For example, there is still a limited body of research on the holistic assessment of nanoformulation shells' fate in soil and in the environment after release, as well as redistribution within plants after absorption, with no studies on human or environmental exposure.

Selective Separation of 1-Butanol from Aqueous Solution through Pervaporation Using PTSMP-Silica Nano Hybrid Membrane.

In this work, a poly(1-trimethylsilyl-1-propyne) (PTMSP) mixed-matrix membrane was fabricated for the selective removal of 1-butanol from aqueous solutions through pervaporation. Silica nanoparticles (SNPs), which were surface-modified with surfactant hexadecyltrimethylammonium bromide (CTAB), were incorporated into the structure of the membrane. The modified membrane was characterized by thermogravimetry-differential scanning calorimetry (TG-DSC), contact angle measurements, and scanning electron microscope (SEM) analysis. It was found that the surface hydrophobicity of the membrane was improved when compared to neat PTMSP by contact angle measurement. It was confirmed by SEM analysis that a uniform distribution of surface-modified SNPs throughout the PTMSP membrane was achieved. The thermogravimetric analysis detected the thermal degradation of the modified PTMSP at 370 °C, which is comparable to neat PTMSP. The pervaporation measurements showed a maximum separation factor of 126 at 63 °C for 1.5 w/w% 1-butanol in the feed. The maximum total flux of approximately 1.74 mg·cm-2·min-1 was observed with the highest inspected temperature of 63 °C and at the 1-butanol concentration in the feed 4.5 w/w%. The pervaporation transients showed that the addition of the surface-modified SNPs significantly enhanced the diffusivity of 1-butanol in the composite compared to the neat PTMSP membrane. This improvement was attributed to the influence of the well-dispersed SNPs in the PTMSP matrix, which introduced an additional path for diffusivity.