Carrier Systems for Advanced Drug Delivery: Improving Drug Solubility/Bioavailability and Administration Routes.

The disadvantages of some conventional drugs, including their low bioavailability, poor targeting efficiency, and important side effects, have led to the rational design of drug delivery systems. In particular, the introduction of drug delivery systems is a potential approach to enhance the uptake of therapeutic agents and deliver them at the right time and in the right amount of concentration at the required site, as well as open new strategies for effective illness treatment. In this review, we provide a basic understanding of drug delivery systems with an emphasis on the use of cyclodextrin-, polymer- and surfactant-based delivery systems.

Analysis of the Efficiency of Antioxidants in Inhibiting Lipid Oxidation in Terms of Characteristic Kinetic Parameters.

In this work, we aim to find physical evidence demonstrating the crucial role that the effective concentration of antioxidants (AOs) present at the interfacial region of emulsions has in controlling the inhibition of the lipid oxidation reaction. We prepared a series of antioxidants of different hydrophobicities derived from chlorogenic and protocatechuic acids. We first monitored, in intact emulsions, the (sigmoidal) production of conjugated dienes and determined the corresponding induction times, .

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.

Efficiency of δ-Tocopherol in Inhibiting Lipid Oxidation in Emulsions: Effects of Surfactant Charge and of Surfactant Concentration.

Charged interfaces may play an important role in the fate of chemical reactions. Alterations in, for instance, the interfacial acidity of emulsions induced by the charge of the surfactant head group and associated counterions may change the ionization status of antioxidants, modifying their effective concentrations. The chemical reactivity between interfacial reactants and charged species of opposite charge (protons, metallic ions, etc.

Partitioning of Antioxidants in Edible Oil-Water Binary Systems and in Oil-in-Water Emulsions.

In recent years, partitioning of antioxidants in oil-water two-phase systems has received great interest because of their potential in the downstream processing of biomolecules, their benefits in health, and because partition constant values between water and model organic solvents are closely related to important biological and pharmaceutical properties such as bioavailability, passive transport, membrane permeability, and metabolism. Partitioning is also of general interest in the oil industry. Edible oils such as olive oil contain a variety of bioactive components that, depending on their partition constants, end up in an aqueous phase when extracted from olive fruits.

Molecular Design of Interfaces of Model Food Nanoemulsions: A Combined Experimental and Theoretical Approach.

The composition and structure of the interfacial region of emulsions frequently determine its functionality and practical applications. In this work, we have integrated theory and experiments to enable a detailed description of the location and orientation of antioxidants in the interfacial region of olive-oil-in-water nanoemulsions (O/W) loaded with the model gallic acid (GA) antioxidant. For the purpose, we determined the distribution of GA in the intact emulsions by employing the well-developed pseudophase kinetic model, as well as their oxidative stability.

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.

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.

Unexpected Antioxidant Efficiency of Chlorogenic Acid Phenolipids in Fish Oil-in-Water Nanoemulsions: An Example of How Relatively Low Interfacial Concentrations Can Make Antioxidants to Be Inefficient.

Selecting effective antioxidants is challenging since their efficiency in inhibiting lipid oxidation depends on the rate constants of the chemical reactions involved and their concentration at the reaction site, i.e., at the interfacial region.

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.

Effects of Surfactant Volume Fraction on the Antioxidant Efficiency and on The Interfacial Concentrations of Octyl and Tetradecyl -Coumarates in Corn Oil-in-Water Emulsions.

Surfactants have been used for decades in the food industry for the preparation of lipid-based emulsified food stuffs. They play two main roles in the emulsification processes: first they decrease the interfacial tension between the oil and water, facilitating droplet deformation and rupture; second, they reduce droplet coalescence by forming steric barriers. However, addition of surfactants to binary oil-water mixtures also brings up the formation of three-dimensional interfacial layers, surrounding each emulsion droplet, that significantly alter chemical reactivity.

Modeling Chemical Reactivity at the Interfaces of Emulsions: Effects of Partitioning and Temperature.

Bulk phase chemistry is hardly ever a reasonable approximation to interpret chemical reactivity in compartmentalized systems, because multiphasic systems may alter the course of chemical reactions by modifying the local concentrations and orientations of reactants and by modifying their physical properties (acid-base equilibria, redox potentials, etc.), making them-or inducing them-to react in a selective manner. Exploiting multiphasic systems as beneficial reaction media requires an understanding of their effects on chemical reactivity.

Interfacial kinetics in olive oil-in-water nanoemulsions: Relationships between rates of initiation of lipid peroxidation, induction times and effective interfacial antioxidant concentrations.

Hypothesis: A detailed quantitative description of the effects of antioxidants in inhibiting lipid peroxidation in oil-in-water emulsions can be achieved by determining the relationships between the rates of initiation of the lipid peroxidation reaction, the length of the induction period preceding the propagation step of the radical oxidation process and the effective antioxidant interfacial concentrations.

Experiments: We successfully prepared and characterized a series of olive oil-in-water nanoemulsions and allowed them to spontaneously oxidize. Their oxidative stability was evaluated by carrying out in the presence, and absence, of antioxidants derived from gallic acid, by monitoring the formation of primary oxidation products with time, by determining the corresponding induction periods, and by determining the effective interfacial concentrations of the antioxidants in the intact emulsions.

Effects of the Reactive Moiety of Phenolipids on Their Antioxidant Efficiency in Model Emulsified Systems.

Our previous research was focused on the effects of hydrophobicity on the antioxidant (AO) efficiency of series of homologous antioxidants with the same reactive moieties. In this work we evaluate the antioxidant efficiency of hydrophobic phenolipids in 4:6 olive oil-in-water emulsions, with different phenolic moieties (derived from caffeic, 4-hydroxycinnamic, dihydrocaffeic acids, tyrosol and hydroxytyrosol), with alkyl chains of 8 and 16 carbons, and compare the antioxidant efficiency with that of the parent compounds. All catecholic phenolipids, in particular the C8 derivatives, have proven to be better antioxidants for the oxidative protection of emulsions than their parental compounds with octyl dihydrocafffeate being the most efficient (16-fold increase in relation to the control).

Nanotechnology-Based Drug Delivery to Improve the Therapeutic Benefits of NRF2 Modulators in Cancer Therapy.

The disadvantages of conventional anticancer drugs, such as their low bioavailability, poor targeting efficacy, and serious side effects, have led to the discovery of new therapeutic agents and potential drug delivery systems. In particular, the introduction of nano-sized drug delivery systems (NDDSs) has opened new horizons for effective cancer treatment. These are considered potential systems that provide deep tissue penetration and specific drug targeting.

Polyphenolic Antioxidants in Lipid Emulsions: Partitioning Effects and Interfacial Phenomena.

The autoxidation of lipids in complex systems such as emulsions or biological membranes, although known to occur readily and to be associated with important pathological events, is lacking in quantitative data in spite of the huge efforts that have been made in attempting to unravel the complex mechanisms of lipid oxidation and its inhibition by antioxidants. Lipids are present as oil-in-water emulsions in many foods and pharmaceutical formulations, and the prevalent role of the interfacial region is critical to understand the antioxidant behavior and to correctly interpret antioxidant efficiencies. The aim of this review is to summarize the current knowledge on the chemical fate of antioxidants before they react with peroxyl radicals.

Interfacial Concentrations of Hydroxytyrosol Derivatives in Fish Oil-in-Water Emulsions and Nanoemulsions and Its Influence on Their Lipid Oxidation: Droplet Size Effects.

Reports on the effect of droplet size on the oxidative stability of emulsions and nanoemulsions are scarce in the literature and frequently contradictory. Here, we have employed a set of hydroxytyrosol (HT) esters of different hydrophobicity and fish oil-in-water emulsified systems containing droplets of different sizes to evaluate the effect of the droplet size, surfactant, (Φ) and oil (Φ) volume fractions on their oxidative stability. To quantitatively unravel the observed findings, we employed a well-established pseudophase kinetic model to determine the distribution and interfacial concentrations of the antioxidants (AOs) in the intact emulsions and nanoemulsions.

Exploring the Use of as Natural Source of Bioactive Compounds with Antioxidant Activity to Prevent Lipid Oxidation of Fish Oil-In-Water Emulsions.

The current industrial requirements for food naturalness are forcing the development of new strategies to achieve the production of healthier foods by replacing the use of synthetic additives with bioactive compounds from natural sources. Here, we investigate the use of plant tissue culture as a biotechnological solution to produce plant-derived bioactive compounds with antioxidant activity and their application to protect fish oil-in-water emulsions against lipid peroxidation. The total phenolic content of plant extracts ranges from 3.

Synthesis, In Vitro Antioxidant Properties and Distribution of a New Cyanothiophene-Based Phenolic Compound in Olive Oil-In-Water Emulsions.

We synthesized and determined the antioxidant activity and distribution of a new cyanothiophene-based compound, -(3-cyano-4,5,6,7-tetrahydrobenzo[]thiophen-2-yl)-3,5-dihydroxybenzamide (SIM-53B), in intact stripped olive oil-in-water emulsion. The in vitro antioxidant properties of SIM-53B were evaluated and compared to those for Trolox and resveratrol. Addition of an emulsifier (Tween 20) creates a narrow region, the aqueous-oil interface, and the distribution of SIM-53B can be described by two partition constants: (between aqueous/interfacial regions) and (between oil/interfacial regions).

Effects of droplet size on the interfacial concentrations of antioxidants in fish and olive oil-in-water emulsions and nanoemulsions and on their oxidative stability.

Hypothesis: One fundamental and unsolved question in colloid chemistry, and also in the food industry, is whether molecular distributions, specifically the interfacial concentrations of antioxidants (AO), are independent of the droplet sizes. Pseudophase kinetic models, widely employed to interpret chemical reactivity in colloidal systems and to determine antioxidant distributions, assume that they are independent.

Experiments: To prove, or discard, the above hypothesis, we prepared and characterized a series of olive and fish oil-in-water nanoemulsions with different droplet sizes, carried out a kinetic study to evaluate their oxidative stability, both in the presence and absence of gallic acid (GA), and determined its interfacial concentrations.

Influence of AO chain length, droplet size and oil to water ratio on the distribution and on the activity of gallates in fish oil-in-water emulsified systems: Emulsion and nanoemulsion comparison.

The distribution of a homologous series of polyphenol derivatives of increasing lipophilicity has been determined in fish oil-in-water emulsions and nanoemulsions by the pseudophase model. One of the hypotheses on which the pseudophase model is based, is that its application is independent of the size of emulsion droplets. In agreement with our hypothesis, results showed that the smaller droplet size found in nanoemulsions does not affect partition constants of gallic acid (GA) and its esters.

Cyclodextrin-Elicited Suspension Cultured Cells: Enhancement of the Production of Bioactive Compounds.

The rates of production of secondary metabolites obtained by employing conventional plant breeding may be low for practical purposes. Thus, innovative approaches for increasing their rates of production are being developed. Here, we propose the use of elicited plant suspension cultured cells (PSCC) with cyclodextrins (CDs) as an alternative method for the production of bioactive compounds from species.

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 (k) by 2.

Enhancing the fraction of antioxidants at the interfaces of oil-in-water emulsions: A kinetic and thermodynamic analysis of their partitioning.

Hypothesis: The distribution of antioxidants (AOs) in O/W emulsions depends on two partition constants, that between oil-interfacial (P), and that between the aqueous-interfacial (P) regions, that need to be determined in the unbroken emulsion to prevent disruptions of the present equilibria. Prediction of the effects of temperature on AO partitioning is challenging because may change both P and P in a different extent and the control of their interfacial concentrations is crucial to optimize their antioxidant efficiency. Such effects can be analyzed in the intact emulsions with the aid of a pseudophase kinetic model.

Targeting Antioxidants to Interfaces: Control of the Oxidative Stability of Lipid-Based Emulsions.

The oxidation of lipid-based emulsions and nanoemulsions strongly affects their overall quality and safety. Moreover, introduction of oxidatively unstable emulsions into biological systems either as an energy source in parenteral nutrition or as delivery systems of bioactives may promote oxidation "in situ" leading to the overproduction of reactive oxygen species, initiating new harmful oxidative reactions and increasing the oxidative damage. Addition of antioxidants, AOs, may help to prevent the oxidative degradation of unsaturated lipids.