Kinetics and Mechanism of Camptothecin Release from Transferrin-Gated Mesoporous Silica Nanoparticles through a pH-Responsive Surface Linker.

Stimuli-responsive nanomaterials have emerged as a promising strategy for inclusion in anticancer therapy. In particular, pH-responsive silica nanocarriers have been studied to provide controlled drug delivery in acidic tumor microenvironments. However, the intracellular microenvironment that the nanosystem must face has an impact on the anticancer effect; therefore, the design of the nanocarrier and the mechanisms that govern drug release play a crucial role in optimizing efficacy. Here, we synthesized and characterized mesoporous silica nanoparticles with transferrin conjugated on their surface via a pH-sensitive imine bond (MSN-Tf) to assess camptothecin (CPT) loading and release. The results showed that CPT-loaded MSN-Tf (MSN-Tf@CPT) had a size of ca. 90 nm, a zeta potential of -18.9 mV, and a loaded content of 13.4%. The release kinetic data best fit a first-order model, and the predominant mechanism was Fickian diffusion. Additionally, a three-parameter model demonstrated the drug-matrix interaction and impact of transferrin in controlling the release of CPT from the nanocarrier. Taken together, these results provide new insights into the behavior of a hydrophobic drug released from a pH-sensitive nanosystem.

Tunable Non-Markovianity for Bosonic Quantum Memristors.

We studied the tunable control of the non-Markovianity of a bosonic mode due to its coupling to a set of auxiliary qubits, both embedded in a thermal reservoir. Specifically, we considered a single cavity mode coupled to auxiliary qubits described by the Tavis-Cummings model. As a figure of merit, we define the dynamical non-Markovianity as the tendency of a system to return to its initial state, instead of evolving monotonically to its steady state. We studied how this dynamical non-Markovianity can be manipulated in terms of the qubit frequency. We found that the control of the auxiliary systems affects the cavity dynamics as an effective time-dependent decay rate. Finally, we show how this tunable time-dependent decay rate can be tuned to engineer bosonic quantum memristors, involving memory effects that are fundamental for developing neuromorphic quantum technologies.

Enhanced Efficiency at Maximum Power in a Fock-Darwin Model Quantum Dot Engine.

We study the performance of an endoreversible magnetic Otto cycle with a working substance composed of a single quantum dot described using the well-known Fock-Darwin model. We find that tuning the intensity of the parabolic trap (geometrical confinement) impacts the proposed cycle's performance, quantified by the power, work, efficiency, and parameter region where the cycle operates as an engine. We demonstrate that a parameter region exists where the efficiency at maximum output power exceeds the Curzon-Ahlborn efficiency, the efficiency at maximum power achieved by a classical working substance.

Transfersomes as alternative topical nanodosage forms for the treatment of skin disorders.

Topical drug delivery is a promising approach to treat different skin disorders. However, it remains a challenge mainly due to the nature and rigidity of the nanosystems, which limit deep skin penetration, and the unsuccessful demonstration of clinical benefits; greater penetration by itself, does not ensure pharmacological success. In this context, transfersomes have appeared as promising nanosystems; deformability, their unique characteristic, allows them to pass through the epidermal microenvironment, improving the skin drug delivery. This review focuses on the comparison of transfersomes with other nanosystems (e.g., liposomes), discusses recent therapeutic applications for the topical treatment of different skin disorders and highlights the need for further studies to demonstrate significant clinical benefits of transfersomes compared with conventional therapies.

Carminic Acid Linked to Silica Nanoparticles as Pigment/Antioxidant Bifunctional Excipient for Pharmaceutical Emulsions.

The incorporation of pigments and natural polyphenols into inorganic matrices, resulting in a hybrid material that improves the resistance and chemical stability of the pigments and the antioxidant capacity of the materials, has been of great interest to the pharmaceutical, chemical and food industries. The aim of this work was to prepare and characterize a bifunctional pigment-antioxidant nanomaterial-based carminic acid-decorated solid core-mesoporous shell silica nanoparticles, evaluating its properties as a pigment, its antioxidant capacity and its properties as a chemical stabilizer of emulsions. The chemical stability of oil-in-water (O/W) Pickering emulsions was evaluated determining the stability of vitamin E solubilized in the oil phase. Carminic acid was attached through the action of coupling ethylcarbodiimide hydrochloride (EDC)/N-hydroxysuccinimide (NHS) agents, and the resulting spherical and homogeneous nanoparticles showed a diameter close to 175 nm. A notorious change of emulsion color was observed by the addition of the nanomaterial. Emulsions showed an attractive pink color, and when the pH was adjusted to pH 3 and pH 9, a change in color was observed, analogous to carminic acid in solution. The nanomaterial incorporation also improved chemical stability, decreasing vitamin E consumption to 9.26% of the initial value, demonstrating an important antioxidant effect of the developed nanomaterial.

Nanoantioxidant-Based Silica Particles as Flavonoid Carrier for Drug Delivery Applications.

Nanosystems used in pharmaceutical formulations have shown promising results in enhancing the administration of drugs of difficult formulations. In particular, porous silica nanoparticles have demonstrated excellent properties for application in biological systems; however, there are still several challenges related to the development of more effective and biocompatible materials. An interesting approach to enhance these nanomaterials has been the development of nanoantioxidant carriers. In this work, a hybrid nanoantioxidant carrier based on porous silica nanoplatform with rosmarinic acid antioxidant immobilized on its surface were developed and characterized. Techniques such as dynamic light scattering (DLS), zeta potential, transmission electron microscopy (TEM), N2 adsorption-desorption measurements, differential scanning calorimetry (DSC), Fourier transform-infrared spectroscopy (FT-IR), and 2,2-diphenyl-1-picrylhydrazyl (DPPH●) assay were used to characterize and evaluate the antioxidant activity of nanocarriers. In addition, drug release profile was evaluated using two biorelevant media. The antioxidant activity of rosmarinic acid was maintained, suggesting the correct disposition of the moiety. Kinetic studies reveal that more morin is released in the simulated intestinal fluid than in the gastric one, while an anomalous non-Fickian release mechanism was observed. These results suggest a promising antioxidant nanocarrier suitable for future application in drug delivery.

Silica-based nanosystems for therapeutic applications in the skin.

Aging, exposure to oxidants, infectious pathogens, inflammogens, ultraviolet radiation and other environmental and genetic factors can result in the development of various skin disorders. Despite immense progress being made in dermatological treatments, many skin-associated problems still remain difficult to treat and various therapies have limitations. Progress in silica-based nanomaterials research provides an opportunity to overcome these drawbacks and improve therapies and is a promising tool for inclusion in clinical practice to treat skin diseases. This review focuses on the use of various types of silica nanoparticles with therapeutic applications in various skin disorders. These nanosystems improve treatment efficacy by maintaining or enhancing the effect of several drugs and are useful tools for nanomedicine, pharmaceutical sciences and future clinical applications.

Nature-inspired pyrrolo[2,3-d]pyrimidines targeting the histamine H3 receptor.

Inspired by marine compounds the derivatization of the natural pyrrolo[2,3-d]pyrimidine lead scaffold led to a series of novel compounds targeting the histamine H3 receptor. The focus was set on improved binding towards the receptor and to establish an initial structure-activity relationship for this compound class based on the lead structure (compound V, Ki value of 126 nM). As highest binding affinities were found with 1,4-bipiperidines as basic part of the ligands, further optimization was focused on 4-([1,4'-bipiperidin]-1'-yl)-pyrrolo[2,3-d]pyrimidines. Related pyrrolo[2,3-d]pyrimidines that were isolated from marine sponges like 4-amino-5-bromopyrrolo[2,3-d]pyrimidine (compound III), showed variations in halogenation pattern, though in a next step the impact of halogenation at 2-position was evaluated. The chloro variations did not improve the affinity compared to the dehalogenated compounds. However, the simultaneous introduction of lipophilic cores with electron-withdrawing substitution patterns in 7-position and dehalogenation at 2-position (11b, 12b) resulted in compounds with significantly higher binding affinities (Ki values of 7 nM and 6 nM, respectively) than the initial lead structure compound V. The presented structures allow for a reasonable structure-activity relationship of pyrrolo[2,3-d]pyrimidines as histamine H3 receptor ligands and yielded novel lead structures within the natural compound library against this target.

Development and Characterization of Florfenicol-Loaded BSA Nanoparticles as Controlled Release Carrier.

Florfenicol (FLO) is a broad-spectrum fluorinated antibiotic used for the treatment of bacterial diseases such as bovine respiratory disease (BRD) in cattle. FLO is a poorly soluble drug in aqueous solution, and its encapsulation in various nanovehicles has been reported to be less than 30%. In this context, the use of bovine serum albumin (BSA) as a nanocarrier for FLO is an interesting approach. BSA is a biocompatible, biodegradable, nontoxic, and nonimmunogenic natural protein, allowing the vehiculization of hydrophilic and hydrophobic drugs with a well-tolerated administration. The present work focuses on the fabrication and characterization of florfenicol-loaded BSA (FLO-BSA NPs), incorporation efficiency, and in vitro release pattern. FLO-BSA NPs nanoparticles were successfully obtained by a simple, low-cost and in a few steps method. The physicochemical properties of the obtained nanoparticles such as size (~ 120 nm), polydispersity index (0.04), and zeta potential (approximately - 40 mV) suggest a high colloidal stability and suitable characteristics for drug delivery. The drug loading reveals a high incorporation of florfenicol in the nanoparticles, in which 33.6 molecules of FLO are encapsulated per each molecule of BSA. The in vitro release profile exhibits an initial stage characterized by the burst effect and then a prolonged release of FLO from the albumin matrix, which is compatible with the Higuchi model and which follows a Fickian diffusion. The results together suggest a suitable tool for future investigations in drug delivery field in order to use this nanomaterial in food, pharmaceutical, and veterinary industry.

Limitations and Opportunities in Topical Drug Delivery: Interaction Between Silica Nanoparticles and Skin Barrier.

The first limiting barrier for the transport in the skin is the stratum corneum; different strategies have been developed to overcome this barrier, including chemical enhancers. However, these penetration enhancers have limitations, including toxic adverse effects. In this context, research into nanomaterials has provided new tools to increase the residence time of drugs by generating a reservoir, increasing the specificity of drugs and reducing their adverse effects, and improving the penetration of drugs that are difficult to formulate. Silica nanoparticles have been proposed as suitable nanocarriers for skin delivery. Unfortunately, the mechanisms involved in the interaction, transport and fate of silica nanoparticles in the skin have not been fully investigated. This paper reviews significant findings about the interaction between silica-based nanocarriers and the skin. First, this review focuses on the properties and functions of the skin, the skin penetration properties of silica nanoparticles, their synthesis strategies and their toxicity. Finally, advances and evidence on the application of silica nanocarriers in skin drug delivery are provided, in which the use of nanoparticles increases the stability and solubility of the bioactive compound, enhancing its performance, act as penetrator enhancer and improving controlled release. Thus, improving the treatment of some skin disorders.

Phytoestrogen coumestrol: Antioxidant capacity and its loading in albumin nanoparticles.

Coumestrol is a polyphenol with promising therapeutic applications as phytoestrogen, antioxidant and potential cancer chemoprevention agent. The presence of two hydroxyl groups on its chemical structure, with orientation analogous to estradiol, is responsible of both, its antioxidant capacity and its estrogenic activity. However, several studies show that the interaction of polyphenols with food and plasma proteins reduces their antioxidant efficacy. We studied the interaction of coumestrol with bovine serum albumin protein (BSA) by fluorescence spectroscopy and circular dichroism techniques, and the effect of this interaction on its antioxidant activity as a hydroxyl radical scavenger. In addition, coumestrol antioxidant capacity profile using different assays (DPPH, ORAC-FL and ORAC-EPR) was studied. To explain its reactivity we used several methodologies, including DFT calculations, to define its antioxidant mechanism. Coumestrol antioxidant activity unveiled interesting antioxidant properties. BSA interaction with coumestrol reduces significantly photolytic degradation in several media thus preserving its antioxidant properties. Results suggest no significant changes in BSA structure and activity when interacting with coumestrol. Furthermore, this interaction is stronger than for other phytoestrogens such as daidzein and genistein. Considering our promising results, we reported for the first time the fabrication and characterization of coumestrol-loaded albumin nanoparticles. The resulting spherical and homogeneous nanoparticles showed a diameter close to 96 nm. The coumestrol incorporation efficiency in BSA NPs was 22.4%, which is equivalent to 3 molecules of coumestrol for every 10 molecules of BSA.

Antioxidant Nanomaterial Based on Core⁻Shell Silica Nanospheres with Surface-Bound Caffeic Acid: A Promising Vehicle for Oxidation-Sensitive Drugs.

The design of efficient, biocompatible, and easily prepared vehicles for drug delivery is a subject of great interest for medicine and pharmaceutical sciences. To achieve the above goals, surface functionalization is critical. Here, we report a hybrid nanocarrier consisting of core⁻shell silica nanospheres and the antioxidant caffeic acid linked to the surface, to evaluate their in vitro antioxidant capacity, their capability to protect oxidation-sensitive compounds incorporated in nanoparticles, and to study the interaction with bovine serum albumin protein. The results show that the radical-scavenging activity of immobilized caffeic acid is attenuated in the silica nanospheres; however, other antioxidant properties such as Fe2+-chelating activity and singlet oxygen quenching are enhanced. In addition, caffeic acid is protected from binding to proteins by the nanoparticle, suggesting that this nanosystem is more likely to maintain the antioxidant activity of caffeic acid in biological media. Finally, the natural antioxidant barrier on the nanocarrier is able to delay the degradation of a compound incorporated into this nanovehicle. Considering all findings, this work proposes a suitable tool for pharmaceutical and cosmetic industries as an antioxidant nanocarrier for oxidation-sensitive drugs.

Quantum Mechanical Engine for the Quantum Rabi Model.

We consider a purely mechanical quantum cycle comprised of adiabatic and isoenergetic processes. In the latter, the system interacts with an energy bath keeping constant the expectation value of the Hamiltonian. In this work, we study the performance of the quantum cycle for a system described by the quantum Rabi model for the case of controlling the coupling strength parameter, the resonator frequency, and the two-level system frequency. For the cases of controlling either the coupling strength parameter or the resonator frequency, we find that it is possible to closely approach to maximal unit efficiency when the parameter is sufficiently increased in the first adiabatic stage. In addition, for the first two cases the maximal work extracted is obtained at parameter values corresponding to high efficiency, which constitutes an improvement over current proposals of this cycle.

An HPLC Method for the Determination of Isoflavones and the Evaluation of Their Antioxidant Capacity in Both Homogeneous and Microheterogeneous Systems.

In this work, we developed an HPLC method to simultaneously quantify and hence evaluate the stability, distribution, and antioxidant capacity of six isoflavones: genistein, genistin, daidzein, daidzin, glycitin, and biochanin A. Isoflavones have been described as having an important estrogenic activity to treat menopausal symptoms and can reduce postmenopausal bone loss and also participate in the prevention of cardiovascular diseases. These beneficial properties are believed derived from their capacity to act as free-radical scavengers. Isoflavones are formulated in capsules and creams and also can be used as antioxidants in liposomes. HPLC separation was achieved on an Agilent Hypersil ODS C18 column. The mobile phase consisted of 0.02-0.2% orthophosphoric acid in water-acetonitrile with gradient elution. The diode array detector was operated at 260 nm. The hydrophobicity of isoflavones was determined through their distribution in octanol-buffer. These results allowed us to establish a relation between chemical structure, pKa, lipophilicity, and the characteristics of the dispersion medium. Photolysis of hydrogen peroxide was used to measure the HO• scavenging capability of isoflavones. In liposomes, the order of reactivity of the studied compounds was genistein > biochanin A > genistin > daidzein > daidzin > glycitin.

Morin Flavonoid Adsorbed on Mesoporous Silica, a Novel Antioxidant Nanomaterial.

Morin (2´,3, 4´,5,7-pentahydroxyflavone) is a flavonoid with several beneficial health effects. However, its poor water solubility and it sensitivity to several environmental factors avoid its use in applications like pharmaceutical and cosmetic. In this work, we synthetized morin-modified mesoporous silica nanoparticles (AMSNPs-MOR) as useful material to be used as potential nanoantioxidant. To achieve this, we characterized its adsorption kinetics, isotherm and the antioxidant capacity as hydroxyl radical (HO•) scavenger and singlet oxygen (1O2) quencher. The experimental data could be well fitted with Langmuir, Freundlich and Temkin isotherm models, besides the pseudo-second order kinetics model. The total quenching rate constant obtained for singlet oxygen deactivation by AMSNPs-MOR was one order of magnitude lower than the morin rate constant reported previously in neat solvents and lipid membranes. The AMSNPs-MOR have good antioxidant properties by itself and exhibit a synergic effect with morin on the antioxidant property against hydroxyl radical. This effect, in the range of concentrations studied, was increased when the amount of morin adsorbed increased.

Flavonoids in Microheterogeneous Media, Relationship between Their Relative Location and Their Reactivity towards Singlet Oxygen.

In this work, the relationship between the molecular structure of three flavonoids (kaempferol, quercetin and morin), their relative location in microheterogeneous media (liposomes and erythrocyte membranes) and their reactivity against singlet oxygen was studied. The changes observed in membrane fluidity induced by the presence of these flavonoids and the influence of their lipophilicity/hydrophilicity on the antioxidant activity in lipid membranes were evaluated by means of fluorescent probes such as Laurdan and diphenylhexatriene (DPH). The small differences observed for the value of generalized polarization of Laurdan (GP) curves in function of the concentration of flavonoids, indicate that these three compounds promote similar alterations in liposomes and erythrocyte membranes. In addition, these compounds do not produce changes in fluorescence anisotropy of DPH, discarding their location in deeper regions of the lipid bilayer. The determined chemical reactivity sequence is similar in all the studied media (kaempferol < quercetin < morin). Morin is approximately 10 times more reactive than quercetin and 20 to 30 times greater than kaempferol, depending on the medium.

Changes in the sorption, desorption, distribution, and availability of copper, induced by application of sewage sludge on Chilean soils contaminated by mine tailings.

The effect of mine tailings and sewage sludge was evaluated on sorption, desorption, availability and distribution of copper in two soils, one high (sandy soil) and one low in copper (clay soil). In both soils contaminated by mine tailings the copper sorption capacity and the affinity of the substrate for the metal decreased substantially compared to the uncontaminated soils, however, the sorption remained always high in the clay soil substrates. In the substrates with sandy soil, the high Cu content and lower clay content were determining factors in the lower magnitude of the sorption. Similarly, metal desorption was closely related to these two parameters, and it was higher in clay soil with lower pH. In general, the application of sewage sludge favored the sorption of Cu in soils contaminated and uncontaminated with mine tailings, and in all cases desorption decreased, an effect that remained for at least 30 days. Simple extraction of Cu with CaCl2 and diethylenetriaminepentaacetic acid gave contradictory results, so a careful choice of the procedure is required, depending on the level of metal in the soil and on the acting principle of the extracting agent. In that relation, more complete information on the changes in the metal forms was obtained by application of the sequential extraction procedure proposed by the European Community Bureau of Reference.