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.

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.) is usually interpreted in terms of pseudophase ion-exchange models, treating the distribution of charged species in terms of partitioning and ion exchange. Here, we focus on analyzing the effects of charged interfaces on the oxidative stability of soybean oil-in-water (o/w) emulsions prepared with anionic (sodium dodecyl sulfate, SDS), cationic (cetyltrimethylammonium bromide, CTAB) and neutral (Tween 20) surfactants, and some of their mixtures, in the presence and absence of δ-tocopherol (δ-TOC). We have also determined the effective concentrations of δ-TOC in the oil, interfacial and aqueous regions of the intact emulsions. In the absence of δ-TOC, the relative oxidative stability order was CTAB < TW20 ~ TW20/CTAB < SDS. Surprisingly, upon the addition of δ-TOC, the relative order was SDS ≈ TW20 << TW20/CTAB < CTAB. These apparently surprising results can be rationalized in terms of the nice correlation that exists between the relative oxidative stability and the effective interfacial concentrations of δ-TOC in the various emulsions. The results emphasize the importance of considering the effective interfacial concentrations of antioxidants in interpreting their relative efficiency in emulsions.

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. Frequently, waste waters are subsequently discarded, but their recovery would allow for obtaining extracts with antioxidant and/or biological activities, adding commercial value to the wastes and, at the same time, would allow for minimizing environmental risks. Thus, given the importance of partitioning antioxidants, in this manuscript, we review the background theory necessary to derive the relevant equations necessary to describe, quantitatively, the partitioning of antioxidants (and, in general, other drugs) and the common methods for determining their partition constants in both binary (PWOIL) and multiphasic systems composed with edible oils. We also include some discussion on the usefulness (or not) of extrapolating the widely employed octanol-water partition constant (PWOCT) values to predict PWOIL values as well as on the effects of acidity and temperature on their distributions. Finally, there is a brief section discussing the importance of partitioning in lipidic oil-in-water emulsions, where two partition constants, that between the oil-interfacial, POI, and that between aqueous-interfacial, PwI, regions, which are needed to describe the partitioning of antioxidants, and whose values cannot be predicted from the PWOIL or the PWOCT ones.

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. We also determined, by employing an in silico design, the radial distribution functions of GA to gain insights on its insertion depth and on its orientation in the interfacial region. Both theoretical and experimental methods provide comparable and complementary results, indicating that most GA is located in the interfacial region (~81.2%) with a small fraction in the aqueous (~18.82%). Thus, GA is an effective antioxidant to inhibit lipid oxidation in emulsions not only because of the energy required for its reaction with peroxyl radical is much lower than that between the peroxyl radical and the unsaturated lipid but also because its effective concentration in the interfacial region is much higher than the stoichiometric concentration. The results demonstrate that the hybrid approach of experiments and simulations constitutes a complementary and useful pathway to design new, tailored, functionalized emulsions to minimize lipid oxidation.

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.

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.

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. Accumulation of antioxidants at the interface of emulsions is key to modulate their efficiency in inhibiting lipid oxidation but its control was not well understood, especially in emulsions. It can be optimized by modifying the physicochemical properties of antioxidants or the environmental conditions. In this work, we analyze the effects of surfactant concentration, droplet size, and oil to water ratio on the effective interfacial concentration of a set of chlorogenic acid (CGA) esters in fish oil-in-water (O/W) emulsions and nanoemulsions and on their antioxidant efficiency. A well-established pseudophase kinetic model is used to determine in the intact emulsified systems the effective concentrations of the antioxidants (AOs). The relative oxidative stability of the emulsions is assessed by monitoring the formation of primary oxidation products with time. Results show that the concentration of all AOs at the interfacial region is much higher (20-90 fold) than the stoichiometric one but is much lower than those of other phenolipid series such as caffeic or hydroxytyrosol derivatives. The main parameter controlling the interfacial concentration of antioxidants is the surfactant volume fraction, ΦI, followed by the O/W ratio. Changes in the droplet sizes (emulsions and nanoemulsions) have no influence on the interfacial concentrations. Despite the high radical scavenging capacity of CGA derivatives and their being concentrated at the interfacial region, the investigated AOs do not show a significant effect in inhibiting lipid oxidation in contrast with what is observed using other series of homologous antioxidants with similar reactivity. Results are tentatively interpreted in terms of the relatively low interfacial concentrations of the antioxidants, which may not be high enough to make the rate of the inhibition reaction faster than the rate of radical propagation.

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.

Effects of Surfactant Volume Fraction on the Antioxidant Efficiency and on The Interfacial Concentrations of Octyl and Tetradecyl p-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. This is the case, for instance, in the inhibition reaction between antioxidants and the lipid radicals formed in the course of the spontaneous oxidation reaction of unsaturated lipids, which are commonly employed in the preparation of food-grade emulsions. The rate of the inhibition reaction depends on the effective concentrations of antioxidants, which are mostly controlled by the amount of surfactant employed in the preparation of the emulsion. In this work, we analyze the effects of the surfactant Tween 20 on the oxidative stability and on the effective concentrations of two model antioxidants derived from cinnamic acid, determining their interfacial concentrations in the intact emulsions to avoid disrupting the existing equilibria and biasing results. For this purpose, a recently developed methodology was employed, and experimental results were interpreted on the grounds of a pseudophase kinetic model.

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. Chemical reactions in multiphasic systems follow the same laws as in bulk solution, and the measured or observed rate constant of bimolecular reactions can be expressed, under dynamic equilibrium conditions, in terms of the product of the rate constant and of the concentrations of reactants. In emulsions, reactants distribute between the oil, water, and interfacial regions according to their polarity. However, determining the distributions of reactive components in intact emulsions is arduous because it is physically impossible to separate the interfacial region from the oil and aqueous ones without disrupting the existing equilibria and, therefore, need to be determined in the intact emulsions. The challenge is, thus, to develop models to correctly interpret chemical reactivity. Here, we will review the application of the pseudophase kinetic model to emulsions, which allows us to model chemical reactivity under a variety of experimental conditions and, by carrying out an appropriate kinetic analysis, will provide important kineticparameters.

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. FINDINGS: Results show that both, the length of the induction periods and the antioxidant interfacial concentrations change concomitantly, increasing with the hydrophobicity of the antioxidant up to a maximum at the octyl derivative; longer aliphatic chains decrease their efficiency. The ratio between the interfacial antioxidant concentration and the induction period remains constant independently of the antioxidant, demonstrating that the effective concentrations of antioxidant at the interface control their efficiencies in 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). To understand the importance of some factors on the antioxidant efficiency of compounds in emulsions, Pearson's correlation analysis was carried out between antioxidant activity and the first anodic potential (Epa), reducing capacity (FRAP value), DPPH radical scavenging activity (EC50) and the concentration of antioxidants in each region of the emulsified system. Results confirm the importance of the effective concentration of AOs in the interfacial region (AOI) (ρ = 0.820) and of the Epa (ρ = -0.677) in predicting their antioxidant efficiency in olive oil-in-water emulsions.

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. Many researchers highlighted the predominant role of interfaces, and although some attempts have been made to understand their role, in most instances, they were essentially qualitative and based on putative hypotheses. It is only recently that quantitative reports have been published. Indeed, knowledge on the effects of relevant experimental variables on the effective concentrations of antioxidants is necessary for a successful design of alternate, effective antioxidative solutions.

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. On the other hand, nuclear factor erythroid 2-related factor 2 (NRF2)-based anticancer treatment approaches have attracted tremendous attention and produced encouraging results. However, the lack of effective formulation strategies is one of the factors that hinder the clinical application of NRF2 modulators. In this review, we initially focus on the critical role of NRF2 in cancer cells and NRF2-based anticancer treatment. Subsequently, we review the preparation and characterization of NDDSs encapsulating NRF2 modulators and discuss their potential for cancer therapy.

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, (ΦI) and oil (ΦO) 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. Results show that there is a direct correlation between antioxidant efficiency and the concentration of the AOs in the interfacial region, which is much higher (20-200 fold) than the stoichiometric one. In both emulsified systems, the highest interfacial concentration and the highest antioxidant efficiency was found for hydroxytyrosol octanoate. Results clearly show that the principal parameter controlling the partitioning of antioxidants is the surfactant volume fraction, ΦI, followed by the O/W ratio; meanwhile, the droplet size has no influence on their interfacial concentrations and, therefore, on their antioxidant efficiency. Moreover, no correlation was seen between droplet size and oxidative stability of both emulsions and nanoemulsions.

Exploring the Use of Bryophyllum 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 Bryophyllum plant extracts ranges from 3.4 to 5.9 mM, expressed as gallic acid equivalents (GAE). The addition of Bryophyllum extracts to 4:6 fish oil-in-water emulsions results in a sharp (eight-fold) increase in the antioxidant efficiency due to the incorporation of polyphenols to the interfacial region. In the emulsions, the antioxidant efficiency of extracts increased linearly with concentration and levelled off at 500 µM GAE, reaching a plateau region. The antioxidant efficiency increases modestly (12%) upon increasing the pH from 3.0 to 5.0, while an increase in temperature from 10 to 30 °C causes a six-fold decrease in the antioxidant efficiency. Overall, results show that Bryophyllum plant-derived extracts are promising sources of bioactive compounds with antioxidant activity that can be eventually be used to control lipid oxidation in food emulsions containing (poly)unsaturated fatty acids.

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, N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]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: PWI (between aqueous/interfacial regions) and POI (between oil/interfacial regions). The effects of emulsifier concentration expressed in terms of the volume fraction, ΦI, and O/W ratio were also evaluated on its distribution. SIM-53B is predominantly distributed (>90%) in the interfacial region of 1:9 (O/W) olive oil-in-water emulsions at the lowest emulsifier volume fraction (ΦI = 0.005) and only a small fraction is located in the aqueous (<5%) and the oil (<5%) regions. Besides, the concentration of SIM-53B in the interfacial region of the emulsions is ~170-190-fold higher than the stoichiometric concentration, emphasizing the compartmentalization effects. Results suggest that the emulsifier volume fraction is a key parameter that may modulate significantly its concentration in the interface. Our study suggests that cyanothiophene-based compounds may be interesting additives for potential lipid protection in biomembranes or other lipid-based systems.

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. The antioxidant efficiency of GA and gallates in the emulsified systems used, correlated positively with the concentration of antioxidant at the interfacial region. The increase in the oil/water ratio increased the overall oxidative stability of emulsions but decreased the antioxidant efficiency of the more lipophilic derivatives. This can be assigned to the fact that, increasing the oil phase volume, the interfacial concentration decreased for the more lipophilic antioxidants.

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 (AOI), 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. FINDINGS: Results indicate that a change in the droplet size (80-1300 nm) does not alter the oxidative stability of the nanoemulsions in the absence of GA. Addition of GA increases their oxidative shelf-life and, at constant surfactant volume fraction, ΦI, the oxidative stability and the antioxidant distribution do not depend on the droplet size. Overall, results suggest that the droplet size does not affect the ratio between the rates of radical production and of inhibition by antioxidants, ratio that defines an "efficient" (or inefficient) antioxidant, providing experimental evidence supporting the operative assumption of pseudophase kinetic models.

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 procedures.