Innovative delivery and release systems for antioxidants and other active substances in the treatment of cancer

Cancer is one of the major diseases leading to death worldwide, and the fight against the disease is still challenging. Cancer diseases are usually associated with increased oxidative stress and the accumulation of reactive oxygen and nitrogen species as a result of metabolic alterations or signaling aberrations. While numerous antioxidants exhibit potential therapeutic properties, their clinical efficiency against cancer is limited and even unproven. Conventional anticancer antioxidants and drugs have, among others, the great disadvantage of low bioavailability, poor targeting efficiency, and serious side effects, constraining their use in the fight against diseases. Here, we review the rationale for and recent advances in potential delivery systems that could eventually be employed in clinical research on antioxidant therapy in cancer. We also review some of the various strategies aimed at enhancing the solubility of poorly water-soluble active drugs, including engineered delivery systems such as lipid-based, polymeric, and inorganic formulations. The use of cyclodextrins, micro- and nanoemulsions, and thermosensitive smart liposomes as useful systems for the delivery and release of poorly aqueous-soluble drugs, improving their bioactivity and stability, is also addressed. We also provide some details on their formulation processes and their use in a variety of medical applications. Finally, we briefly cover a case study specifically focused on the use of delivery systems to minimize oral cancer and associated dental problems.Xunta de Galicia | Ref. ED431E 2018/07Universidade de Vigo | Ref. C11Universidade de Vigo | Ref. ABH1-V231Xunta de Galicia | Ref. ED431D 2017/1

Synthesis and characterization of cyclotriphosphazenes containing silicon as single solid-state precursors for the formation of silicon/phosphorus nanostructured materials

The synthesis and characterization of new organosilicon derivatives of N3P3Cl6, N3P3[NH(CH2)3Si(OEt)3]6 (1), N3P3[NH(CH2)3Si(OEt)3]3[NCH3(CH2)3CN]3 (2), and N3P3[NH(CH2)3Si(OEt)3]3[HOC6H4(CH2)CN]3 (3) are reported. Pyrolysis of 1, 2, and 3 in air and at several temperatures results in nanostructured materials whose composition and morphology depend on the temperature of pyrolysis and the substituents of the phosphazenes ring. The products stem from the reaction of SiO2 with P2O5, leading to either crystalline Si5(PO4)6O, SiP2O7 or an amorphous phase as the glass Si5(PO4)6O/3SiO2·2P2O5, depending on the temperature and nature of the trimer precursors. From 1 at 800 °C, core−shell microspheres of SiO2 coated with Si5(PO4)6O are obtained, while in other cases, mesoporous or dense structures are observed. Atomic force microscopy examination after deposition of the materials on monocrystalline silicon wafers evidences morphology strongly dependent on the precursors. Isolated islands of size ∼9 nm are observed from 1, whereas dense nanostructures with a mean height of 13 nm are formed from 3. Brunauer−Emmett−Teller measurements show mesoporous materials with low surface areas. The proposed growth mechanism involves the formation of cross-linking structures and of vacancies by carbonization of the organic matter, where the silicon compounds nucleate. Thus, for the first time, unique silicon nanostructured materials are obtained from cyclic phosphazenes containing silicon

Solid-state synthesis of embedded single-crystal metal oxide and phosphate nanoparticles and in situ crystallization

A new solid state organometallic route to embedded nanoparticle-containing inorganic materials is shown, through pyrolysis of metal-containing derivatives of cyclotriphosphazenes. Pyrolysis in air and at 800 °C of new molecular precursors gives individual single-crystal nanoparticles of SiP2O7, TiO2, P4O7, WP2O7 and SiO2, depending on the precursor used. High resolution transmission electron microscopy investigations reveal, in most cases, perfect single crystals of metal oxides and the first nanostructures of negative thermal expansion metal phosphates with diameters in the range 2–6 nm for all products. While all nanoparticles are new by this method, WP2O7 and SiP2O7 nanoparticles are reported for the first time. In situ recrystallization formation of nanocrystals of SiP2O7 was also observed due to electron beam induced reactions during measurements of the nanoparticulate pyrolytic products SiO2 and P4O7. The possible mechanism for the formation of the nanoparticles at much lower temperatures than their bulk counterparts in both cases is discussed. Degrees of stabilization from the formation of P4O7 affects the nanocrystalline products: nanoparticles are observed for WP2O7, with coalescing crystallization occurring for the amorphous host in which SiP2O7 crystals form as a solid within a solid. The approach allows the simple formation of multimetallic, monometallic, metal-oxide and metal phosphate nanocrystals embedded in an amorphous dielectric. The method and can be extended to nearly any metal capable of successful coordination as an organometallic to allow embedded nanoparticle layers and features to be deposited or written on surfaces for application as high mobility pyrophosphate lithium–ion cathode materials, catalysis and nanocrystal embedded dielectric layers

Exploring the use of hydroxytyrosol and some of its esters in food-grade nanoemulsions: establishing connection between structure and efficiency

The efficiency of HT and that of some of its hydrophobic derivatives and their distribution and effective concentrations were investigated in fish oil-in-water nanoemulsions. For this purpose, we carried out two sets of independent, but complementary, kinetic experiments in the same intact fish nanoemulsions. In one of them, we monitored the progress of lipid oxidation in intact nanoemulsions by monitoring the formation of conjugated dienes with time. In the second set of experiments, we determined the distributions and effective concentrations of HT and its derivatives in the same intact nanoemulsions as those employed in the oxidation experiments. Results show that the antioxidant efficiency is consistent with the “cut-off” effect—the efficiency of HT derivatives increases upon increasing their hydrophobicity up to the octyl derivative after which a further increase in the hydrophobicity decreases their efficiency. Results indicate that the effective interfacial concentration is the main factor controlling the efficiency of the antioxidants and that such efficiency strongly depends on the surfactant concentration and on the oil-to-water (o/w) ratio employed to prepare the nanoemulsions.Agencia Estatal de Investigación | Ref. PID2022-136443OB-I0

Biochemistry of antioxidants: mechanisms and pharmaceutical applications

Natural antioxidants from fruits and vegetables, meats, eggs and fish protect cells from the damage caused by free radicals. They are widely used to reduce food loss and waste, minimizing lipid oxidation, as well as for their effects on health through pharmaceutical preparations. In fact, the use of natural antioxidants is among the main efforts made to relieve the pressure on natural resources and to move towards more sustainable food and pharmaceutical systems. Alternative food waste management approaches include the valorization of by-products as a source of phenolic compounds for functional food formulations. In this review, we will deal with the chemistry of antioxidants, including their molecular structures and reaction mechanisms. The biochemical aspects will also be reviewed, including the effects of acidity and temperature on their partitioning in binary and multiphasic systems. The poor bioavailability of antioxidants remains a huge constraint for clinical applications, and we will briefly describe some delivery systems that provide for enhanced pharmacological action of antioxidants via drug targeting and increased bioavailability. The pharmacological activity of antioxidants can be improved by designing nanotechnology-based formulations, and recent nanoformulations include nanoparticles, polymeric micelles, liposomes/proliposomes, phytosomes and solid lipid nanoparticles, all showing promising outcomes in improving the efficiency and bioavailability of antioxidants. Finally, an overview of the pharmacological effects, therapeutic properties and future choice of antioxidants will be incorporated.Fundação para a Ciência e Tecnologia | Ref. UIDB/50006/2020Fundação para a Ciência e Tecnologia | Ref. UIDP/50006/202

Adsorption of gallic acid, propyl gallate and polyphenols from Bryophyllum extracts on activated carbon

The adsorption of gallic acid (GA) and propyl gallate (PG) on activated carbon (AC) was studied as a function of the AC mass and temperature. Clean first order behavior was obtained for at least three half-lives and the equilibrium was reached after ∼4 h contact time. An increase in the temperature (T = 20–40 °C) increases their adsorption rate constant values (k1) by 2.5 fold but has a negligible effect on the amount of antioxidant adsorbed per mass of AC at equilibrium. We also analyzed the adsorption process of polyphenols from Bryophyllum extracts and ca 100% of the total amount of the polyphenols in the extract were adsorbed when using 7 mg of AC. Results can be explained on the basis of the Freundlich isotherm but do not fit the Langmuir model. Results suggest that the combination of emerging in vitro plant culture technologies with adsorption on activated carbon can be successfully employed to remove important amounts of bioactive compounds from plant extracts by employing effective, sustainable and environmental friendly proceduresXunta de Galicia | Ref. ED431D 2017/18Xunta de Galicia | Ref. ED431E 2018/07Ministerio de Educación, Cultura y Deporte | Ref. FPU15/04849Xunta de Galicia | Ref. POS-B/2016/01

Distributions of α- and δ-TOCopherol in Intact Olive and Soybean Oil-in-Water Emulsions at Various Acidities: A Test of the Sensitivity of the Pseudophase Kinetic Model

During the last years, the formalism of the pseudophase kinetic model (PKM) has been successfully applied to determine the distributions of antioxidants and their effective interfacial concentrations, and to assess the relative importance of emulsion and antioxidant properties (oil and surfactant nature, temperature, acidity, chemical structure, hydrophilic-liphophilic balance (HLB), etc.) on their efficiency in intact lipid-based emulsions. The PKM permits separating the contributions of the medium and of the concentration to the overall rate of the reaction. In this paper, we report the results of a specifically designed experiment to further test the suitability of the PKM to evaluate the distributions of antioxidants among the various regions of intact lipid-based emulsions and provide insights into their chemical reactivity in multiphasic systems. For this purpose, we employed the antioxidants α- and δ-TOCopherol (α- and δ-TOC, respectively) and determined, at different acidities well below their pKa, the interfacial rate constants kI for the reaction between 16-ArN2+ and α- and δ-TOC, and the antioxidant distributions in intact emulsions prepared with olive and soybean oils. Results show that the effective interfacial concentration of δ-TOC is higher than that of α-TOC in 1:9 (v/v) soybean and 1:9 olive oil emulsions. The effective interfacial concentrations of tocopherols are much higher (15-96-fold) than the stoichiometric concentrations, as the effective interfacial concentrations of both δ-TOC and α-TOC in soybean oil emulsions are higher (2-fold) than those in olive oil emulsions. Overall, the results demonstrate that the PKM grants an effective separation of the medium and concentration effects, demonstrating that the PKM constitutes a powerful non-destructive tool to determine antioxidant concentrations in intact emulsions and to assess the effects of various factors affecting them.Universidade de Vigo | Ref. C11Ministério da Ciência, Tecnologia e Ensino Superior | Ref. UIDB/50006/2020Ministério da Ciência, Tecnologia e Ensino Superior | Ref. UIDP/50006/202

Polyphenols as antioxidants for extending food shelf-life and in the prevention of health diseases: encapsulation and interfacial phenomena

Toxicity caused by the exposure to human-made chemicals and environmental conditions has become a major health concern because they may significantly increase the formation of reactive oxygen species (ROS), negatively affecting the endogenous antioxidant defense. Living systems have evolved complex antioxidant mechanisms to protect cells from oxidative conditions. Although oxidative stress contributes to various pathologies, the intake of molecules such as polyphenols, obtained from natural sources, may limit their effects because of their antioxidant and antimicrobial properties against lipid peroxidation and against a broad range of foodborne pathogens. Ingestion of polyphenol-rich foods, such as fruits and vegetables, help to reduce the harmful effects of ROS, but the use of supramolecular and nanomaterials as delivery systems has emerged as an efficient method to improve their pharmacological and therapeutic effects. Suitable exogenous polyphenolic antioxidants should be readily absorbed and delivered to sites where pathological oxidative damage may take place, for instance, intracellular locations. Many potential antioxidants have a poor bioavailability, but they can be encapsulated to improve their ideal solubility and permeability profile. Development of effective antioxidant strategies requires the creation of new nanoscale drug delivery systems to significantly reduce oxidative stress. In this review we provide an overview of the oxidative stress process, highlight some properties of ROS, and discuss the role of natural polyphenols as bioactives in controlling the overproduction of ROS and bacterial and fungal growth, paying special attention to their encapsulation in suitable delivery systems and to their location in colloidal systems where interfaces play a crucial role.Fundação para a Ciência e a Tecnologia | Ref. UID / QUI / 50006/2019Fundação para a Ciência e a Tecnologia | Ref. POCI-01-0145-FEDER-032492Fundação para a Ciência e a Tecnologia | Ref. SFRH / BD / 100889/2014Xunta de Galicia | Ref. 10TAL314003P

Plant antioxidants in food emulsions

Addition of free radical scavenging antioxidants (AOs) is one of practical strategies controlling the oxidative stability in food emulsions. Attention has been directed toward AOs derived from natural plant extracts with the capacity to improve health and well-being due to lack of consumers’ trust toward synthetic antioxidant in food. Nevertheless, antioxidant efficiency varies widely from one compound to another and the most abundant AOs in our diet are not necessarily those that have the best availability profile at the reaction place with free radicals. In this book chapter, we will provide a state-of-the-art summary of the uses of plant AOs in colloidal systems, ranging from their main structural features to their benefits for the human health and their antioxidant role in controlling the oxidative stress and, particularly, the oxidation of lipid-based food emulsions.Xunta de Galicia | Ref. ED431D-2017/18Ministerio de Educación y Ciencia | Ref. CTQ2006-13969-BQUMinisterio de Educación, Cultura y Deporte | Ref. FPU15/04849Xunta de Galicia | Ref. POS-B/2016/01

OMA -AMO - Casa de la música de Oporto

La investigación de un “objeto arquitectónico” enlaza con los principios teóricos desde los que en ARKRIT-LAB se entiende la crítica la arquitectura: la obra antes que el autor y su descripción antes que su interpretación. Consecuentemente, se propuso estudiar un edificio relevante y considerado de gran impacto teórico y mediático, entrando primero de manera precisa en su respuesta al medio, al material, a la medida, a la morfología y a la misión -metodo M3- y proponiendo después, entre los investigadores del laboratorio diversas actividades: re exionar de manera abierta sobre las condiciones de su “arquitectura”, experimentar el edi cio, rastrear sus antecedentes e investigar en la materia concreta y en las formas utilizadas; actividades que buscaban nuevas realidades que pudieran mostrar otras visiones. En el laboratorio consideramos que como arquitectos y como críticos, no resulta super uo aprender a ver más, a oír más, a sentir más y a pensar más4. El edificio elegido para el curso 2010-2011 fue la “Casa da Musica” de Oporto, proyecto de OMA-Rem Koolhaas, siendo el texto que se convirtió en referencia para la primera aproximación el titulado “Otra Modernidad” de Rafael Moneo. Texto en el que se describe el proyecto como encarnación de los nuevos atributos de la arquitectura contemporánea5. “Otra Modernidad” entendida desde la Modernidad, como frontera considerada por Antonio Miranda como referente de progreso y faro de toda acción arquitectónica. Modernidad como anhelo de una sociedad nueva más justa