Effective Oral Administration of an Antitumorigenic Nanoformulated Titanium Complex

Abstract : Orally administered anticancer drugs facilitate treatment, but the acidic conditions in the stomach often challenge their availability. PhenolaTi is a Ti^IV-based nontoxic anticancer drug with marked in-vivo efficacy. We report that nanoformulation protects phenolaTi from decomposition in stomach-like conditions. This is evidenced by similar NMR characteristics and similar in-vitro cytotoxicity toward murine (CT-26) and human (HT-29) colon cancer cells before and after incubation of nanoformulated phenolaTi (phenolaTi-F) at pH 2, unlike results with the unformulated form of the complex. Furthermore, administration of phenolaTi-F in animal drinking water revealed a notable inhibition of tumor growth in Balb/c and immune-deficient (Nude) mice inoculated with CT-26 and HT-29 cells, respectively. In-vivo efficacy was at least similar to that of the corresponding intraperitoneal treatment with phenolaTi-F and the clinically employed oral drug, capecitabine. No body weight loss or clinical signs of toxicity were evident in the phenolaTi-F-treated animals. These findings demonstrate a new convenient mode of cancer treatment through oral administration by safe titanium-based drugs.     

Biodegradable Amphoteric Surfactants in Titration-Ultrasound Formulation of Oil-in-Water Nanoemulsions: Rational Design,Development, and Kinetic Stability

Amphoteric amphiphilic compounds, due to their unique properties, may represent a group of safe and biocompatible surface-active agents for effective colloidal stabilization of nanoformulations. For this reason, the aim of this work was to develop and characterize the oil-in-water nanoemulsions based on two betaine-derived surfactants with high biodegradability, i.e., cocamidopropyl betaine and coco-betaine. In the first step, we investigated ternary phase diagrams of surfactant-oil-water systems containing different weight ratios of surfactant and oil, as the betaine-type surfactant entity (S), linoleic acid, or oleic acid as the oil phase (O), and the aqueous phase (W) using the titration-ultrasound approach. All the received nanoemulsion systems were then characterized upon droplets size (dynamic light scattering), surface charge (electrophoretic light scattering), and morphology (transmission electron as well as atomic force microscopy). Thermal and spinning tests revealed the most stable compositions, which were subjected to further kinetic stability analysis, including turbidimetric evaluation. Finally, the backscattering profiles revealed the most promising candidate with a size <200 nm for potential delivery of active agents in the future cosmetic, pharmaceutical, and biomedical applications.     

Use of essential oils and phytochemicals against the mycotoxins producing fungi for shelf-life enhancement and food preservation

Mycotoxin-producing fungi are a significant source of crop and food contamination, posing a significant threat to global food safety and security. Essential oils, plant extracts and phytochemicals have emerged as green preservatives to extend the shelf-life of foods due to their unique antimicrobial properties. Unlike conventional synthetic preservatives, they are a sustainable and safe way to preserve food with no or little harmful effects on the environment. Use of nanoformulations containing essential oils and phytochemicals offer enormous potential as a mitigation strategy to lower mycotoxin contamination incidences in food and crop with enhanced release behaviour to efficiently transport them to the target location for a rapid reaction without much impact from environmental variables. Hence, this review overviews various essential oils and phytochemicals utilized through nanoformulations to control the mycotoxigenic fungi, probable mechanism of actions involved as well as emerging mycotoxins and associated safety concerns to ensure food sustainability.     

Exploiting the Thiobarbituric Acid Scaffold for Antibacterial Activity

Thiobarbituric acid (TBA) has been considered a privileged structure for developing antimicrobial agents. Diversity was obtained at positions N and at C5 through acylation, Schiff base formation, Knoevenagel condensation, and thioamide and enamine formation. The present work describes the synthesis of small libraries based on the TBA moiety and above‐mentioned reactions. Preliminary antimicrobial activity screening of the prepared compounds against selected bacteria (both Gram‐positive and ‐negative) showed the best results for the Boc‐Phe‐TBA derivative. These results could be useful for designing and building libraries based on other amino acids with distinct protecting groups.     

ASP-Enzymosomes with Saccharomyces cerevisiae Asparaginase II Expressed in Pichia pastoris: Formulation Design and In Vitro Studies of a Potential Antileukemic Drug

The bacterial enzyme asparaginase is the main treatment option for acute lymphoblastic leukemia. However, it causes side effects, such as immunological reactions, and presents undesirable glutaminase activity. As an alternative, we have been studying asparaginase II from Saccharomyces cerevisiae, coded by ASP3 gene, which was cloned and expressed in Pichia pastoris. The recombinant asparaginase (ASP) presented antileukemic activity and a glutaminase activity 100 times lower in comparison to its asparaginase activity. In this work, we describe the development of a delivery system for ASP via its covalent attachment to functionalized polyethylene glycol (PEG) polymer chains in the outer surface of liposomes (ASP-enzymosomes). This new delivery system demonstrated antiproliferative activity against K562 (chronic myeloid leukemia) and Jurkat (acute lymphocytic leukemia) cell lines similar to that of ASP. The antiproliferative response of the ASP-enzymosomes against the Jurkat cells suggests equivalence to that of the free Escherichia coli commercial asparaginase (Aginasa^®). Moreover, the ASP-enzymosomes were stable at 4 °C with no significant loss of activity within 4 days and retained 82% activity up to 37 days. Therefore, ASP-enzymosomes are a promising antileukemic drug.     

Design and Engineering of “Green” Nanoemulsions for Enhanced Topical Delivery of Bakuchiol Achieved in a Sustainable Manner: A Novel Eco-Friendly Approach to Bioretinol

In the present work, we establish novel “environmentally-friendly” oil-in-water nanoemulsions to enhance the transdermal delivery of bakuchiol, the so-called “bioretinol” obtained from powdered Psoralea corylifolia seeds via a sustainable process, i.e., using a supercritical fluid extraction approach with pure carbon dioxide (SC-CO₂). According to Green Chemistry principles, five novel formulations were stabilized by “green” hybrid ionic surfactants such as coco-betaine—surfactin molecules obtained from coconut and fermented rapeseed meal. Preliminary optimization studies involving three dispersion stability tests, i.e., centrifugation, heating, and cooling cycles, indicated the most promising candidates for further physicochemical analysis. Finally, nanoemulsion colloidal characterization provided by scattering (dynamic and electrophoretic light scattering as well as backscattering), microscopic (transmission electron and confocal laser scanning microscopy), and spectroscopic (UV–Vis spectroscopy) methods revealed the most stable nanocarrier for transdermal biological investigation. In vitro, topical experiments provided on human skin cell line HaCaT keratinocytes and normal dermal NHDF fibroblasts indicated high cell viability upon treatment of the tested formulation with a final 0.02–0.2 mg/mL bakuchiol concentration. This excellent biocompatibility was confirmed by ex vivo and in vivo tests on animal and human skin tissue. The improved permeability and antiaging potential of the bakuchiol-encapsulated rich extract were observed, indicating that the obtained ecological nanoemulsions are competitive with commercial retinol formulations.     

Fabrication and characterization of cytocompatible polypyrrole films inkjet printed from nanoformulations cytocompatible, inkjet-printed polypyrrole films

Inkjet printed polypyrrole (PPy) films with good uniformity and conductivity are fabricated from a stable, printable PPy nanodispersion, and the cytocompatability of these platforms is demonstrated using PC12 cells. This novel approach to fabricating PPy electrodes and films for tissue engineering and cell stimulation is particularly useful where microstructures are required.