Formation Of Host-guest Complexes Research Articles

Dexamethasone-loaded ROS stimuli-responsive nanogels for topical ocular therapy of corneal neovascularization

Dexamethasone (DEX) has been demonstrated to inhibit the inflammatory corneal neovascularization (CNV). However, the therapeutic efficacy of DEX is limited by the poor bioavailability of conventional eye drops and the increased risk of hormonal glaucoma and cataract associated with prolonged and frequent usage. To address these limitations, we have developed a novel DEX-loaded, reactive oxygen species (ROS)-responsive, controlled-release nanogel, termed DEX@INHANGs. This advanced nanogel system is constructed by the formation of supramolecular host-guest complexes by cyclodextrin (CD) and adamantane (ADA) as a cross-linking force. The introduction of the ROS-responsive material, thioketal (TK), ensures the controlled release of DEX in response to oxidative stress, a characteristic of CNV. Furthermore, the nanogel's prolonged retention on the corneal surface for over 8 h is achieved through covalent binding of the integrin β1 fusion protein, which enhances its bioavailability. Cytotoxicity assays demonstrated that DEX@INHANGs was not notably toxic to human corneal epithelial cells (HCECs). Furthermore, DEX@INHANGs has been demonstrated to effectively inhibit angiogenesis in vitro. In a rabbit model with chemically burned eyes, the once-daily topical application of DEX@INHANGs was observed to effectively suppress CNV. These results collectively indicate that the nanomedicine formulation of DEX@INHANGs may offer a promising treatment option for CNV, offering significant advantages such as reduced dosing frequency and enhanced patient compliance.

In Ukrainian

Due to the variety of their forms and properties, silver nanoparticles (AgNPs) are promising for obtaining nanomaterials with various functional applications. Today, regardless of the method of obtaining AgNPs, there is a problem of stabilizing their surface to prevent aggregation, which significantly reduces their activity and prevents uniform distribution during the preparation of nanomaterials. The aim of this work was the synthesis of silver nanoparticles using an oligomeric ionic liquid (OIL) and the study of their structure and antimicrobial properties. In this work, for the first time, an anionic OIL with a hyperbranched structure developed by us was used as a surface stabilizer in the synthesis of AgNPs. The synthesis of AgNPs was carried out by the reduction of Ag ions in the composition of AgNO3 with trisodium citrate in the presence of this OIL. Using the methods ofUV-vis and FTIR spectroscopy, X-ray analysis, electron microscopy and the disc-diffusion method, the peculiarities of the structural organization of AgNPs and their antimicrobial properties were studied. UV-visible spectroscopy data indicate the formation of silver nanoparticles and their spherical or quasi-spherical shape. It was found that there are adsorbed ionic and carbonyl groups on the surface of the formed AgNPs, and the formation of host-guest complexes between OIL and silver ions was revealed using FTIR. The formation of AgNPs and complexes between OIL and silver ions is also confirmed by X-ray diffraction. According to electron microscopy, the size of the synthesized nanoparticles varies from 5 to 16 nm, with an average value of 10.2 nm. This average value is very close to the value of 9.3 nm obtained from the results of X-ray analysis. The synthesized silver nanoparticles showed a very high antimicrobial activity against C. albicans fungi, while the width of the inhibition zone (d) was 34 mm. Also, the AgNPs powder shows very high activity against gram-positive bacteria S. aureus (d = 30 mm) and gram-negative bacteria E. coli (d = 12 mm). The approach developed by us to the synthesis of AgNPs in the presence of OIL as a surface stabilizer with certain functionalization of the latter opens up new opportunities in the synthesis of AgNPs and the preparation of highly dispersed related systems, including functionalized nanocomposite polymer materials with antimicrobial properties.

Chirality Sensing of Cryptochiral Guests with Prism[n]arenes.

Optical chirality sensing has gained significant attention in recent years. Within this field, the quest for stereodynamic chiroptical probes capable of detecting cryptochiral guests presents a formidable challenge. Macrocycles exhibiting planar chirality have emerged as promising candidates for amplifying the chirality of cryptochiral guests. In this study, we demonstrate that the formation of host-guest complexes between cryptochiral molecules and planar chiral prismarenes triggers electronic circular dichroism (ECD) signals via host-guest complexation-induced chirality amplification. The absolute configuration of the most stable chiral macrocyclic host-guest complex has been established by resorting to both exciton model and DFT computations. Furthermore, we demonstrated that this supramolecular chirality sensing system can be employed to determine the enantiomeric composition of scalemic mixtures by measuring the ECD bands intensity. The information described here opens the way for the use of prismarenes as stereodynamic probes for sensing of cryptochiral guests.

Easy and Effective Method for α-CD:N2O Host-Guest Complex Formation.

α-CD:N2O "host-guest" type complexes were formed by a simple solid-gas reaction (N2O sorption into α-CD) under different gas pressures and temperatures. The new N2O inclusion method applied in the present study was compared with the already known technique based on the crystallization of clathrates from a water solution of α-CD saturated with N2O. A maximum storage capacity of 4.5 wt.% N2O was achieved when charging the cyclodextrin from a gas phase. The amount of included gas decreases to 1.3 wt.% when the complex is stored in air at 1 atm and room temperature, analogous to that achieved by the crystallization of α-CD:N2O. Furthermore, it was shown that the external coordination of N2O to either the upper or lower rim of α-CD without hydration water displacement is the preferred mode of binding, due to hydrogen bonds with neighboring -OH groups from the host macrocycle and three of the hydration water molecules nearby. The capacity of α-CD to store N2O and the thermal stability of the α-CD:N2O complex demonstrated promising applications of these types of complexes in food and beverages.

Effect of Crown Ether Additives on the Enhanced Performance of Metallic Bipolar Plates for Proton Exchange Membrane Fuel Cells.

One of the key components of the fuel cell stack is a metallic bipolar plate (MBP) that plays multiple roles, such as current collector, fuel and oxidant distributor, and mechanical support. However, corrosion and consequent metal elution are major drawbacks of the MBP because they diminish the efficiency and power performance of membrane-electrode assemblies (MEAs). Herein, we show that the crown ether (CE) additive can simultaneously inhibit surface corrosion of the MBP and act as a scavenger for eluted metal ions to alleviate contamination of other components. From the electrochemical measurement, high-resolution imaging, and elemental analysis, we have found that the CE undergoes electrolytic decomposition and makes an efficient protective layer in an in situ manner. This layer prevents direct contact between the MBP and electrolyte as well as the dissolution of metal ions into the electrolyte. In addition, we demonstrate that the CE can improve the recovery protocol of the MEA owing to the formation of host-guest complexes between the CE and metal cations. These results provide key insights into the design of high-performance MBPs for proton-exchange membrane fuel cells.

Bidentate boron Lewis acids: synthesis by tin boron exchange reaction and host-guest complex formation.

Four bidentate boron Lewis acids based on the 1,8-diethynylanthracene backbone have been synthesized by a tin-boron exchange reaction with various chloroboranes, yielding the products in good to excellent yields. Complexation experiments of the host compounds with pyridine, pyrimidine and TMEDA demonstrated striking differences in terms of formation and solubility of the supramolecular adducts. The host-guest complexes were investigated by multinuclear NMR spectroscopy and structurally characterized by X-ray diffraction experiments, illustrating the adaptation of the host system upon adduct formation with different neutral guest molecules.

Direct thermodynamic characterization of solid-state reactions by isothermal calorimetry.

Despite the growing importance of solid-state reactions, their thermodynamic characterization has largely remained unexplored. This is in part due to the lack of methodology for measuring the heat effects related to reactions between solid reactants. We address here this gap and report on the first direct thermodynamic study of chemical reactions between solid reactants by isothermal calorimetry. Three reaction classes, cationic host-guest complex formation, molecular co-crystallization, and Baeyer-Villiger oxidation were investigated, showcasing the versatility of the devised methodology to provide detailed insight into the enthalpy changes related to various reactions. The reliability of the method was confirmed by correlation with the values obtained via solution calorimetry using Hess's law. The thermodynamic characterization of solid-state reactions described here will enable a deeper understanding of the factors governing solid-state processes.

Switchable Metal-Ion Selectivity in Sulfur-Functionalised Pillar[5]arenes and Their Host-Guest Complexes.

Nucleophilic substitution of pertosylated pillar[5]arene (P-OTs) with commercially available sulfur containing nucleophiles (KSCN, KSAc, and thiophenol), yields a series of sulfur-functionalised pillar[5]arenes. DLS results and SEM images imply that these pillararene macrocycles self-assemble in acetonitrile solution, while X-ray crystallographic evidence suggests solvent-dependent assembly in the solid state. The nature of the sulfur substituents decorating the rim of the pillararene controls binding affinities towards organic guest encapsulations within the cavity and dictates metal-ion binding properties through the formation of favorable S-M2+ coordination bonds outside the cavity, as determined by 1 H NMR and fluorescence spectroscopic experiments. Addition of a dinitrile guest containing a bis-triazole benzene spacer (btn) induced formation of pseudorotaxane host-guest complexes. Fluorescence emission signals from these discrete macrocycles were significantly attenuated in the presence of either Hg2+ or Cu2+ in solution. Analogous titrations utilizing the corresponding pseudorotaxanes alter the binding selectivity and improve fluorescence sensing sensitivity. In addition, preliminary liquid-liquid extraction studies indicate that the macrocycles facilitate the transfer of Cu2+ from the aqueous to the organic phase in comparison to extraction without pillar[5]arene ligands.

Adsorption Mechanism of Benzene Derivatives by Pagoda[n]arenes.

Despite the widespread use in industrial production, benzene derivatives are harmful to both human beings and the environment.The control of these substances has become animportant subjectof scientific researches. This study introduces a new approach for adsorption and separation of benzene derivatives utilizing supramolecular materials based on pagoda[n]arene. Density functional theory (DFT) calculations were employed to investigate the molecular recognition mechanism of benzene derivatives by pagoda[4]arenes and pagoda[5]arenes(Pa[4]As and Pa[5]As). It was discovered that Pa[4]As and Pa[5]Ascan effectively accommodate benzene derivatives through non-covalent interactions, leading to the formation of stable host-guest complexes. Additionally, molecular dynamics (MD) simulations revealed that both crystalline and non-crystalline supramolecular aggregates of Pa[4]As and Pa[5]Aspossess the ability to adsorb benzene derivatives and maintain the stability of the adsorption. Moreover, increasing the temperature causes benzene derivativesto desorption from the adsorbing aggregates, and thus to achieve reutilization of the adsorbent materials.

Electrochemically Controlled Release from a Thin Hydrogel Layer.

In this study, we present a thermoresponsive thin hydrogel layer based on poly(N-isopropylacrylamide), functionalized with β-cyclodextrin groups (p(NIPA-βCD)), as a novel electrochemically controlled release system. This thin hydrogel layer was synthesized and simultaneously attached to the surface of a Au quartz crystal microbalance (QCM) electrode using electrochemically induced free radical polymerization. The process was induced and monitored using cyclic voltammetry and a quartz crystal microbalance with dissipation monitoring (QCM-D), respectively. The properties of the thin layer were investigated by using QCM-D and scanning electron microscopy (SEM). The incorporation of β-cyclodextrin moieties within the polymer network allowed rhodamine B dye modified with ferrocene (RdFc), serving as a model metallodrug, to accumulate in the p(NIPA-βCD) layer through host-guest inclusion complex formation. The redox properties of the electroactive p(NIPA-βCD/RdFc) layer and the dissociation of the host-guest complex triggered by changes in the oxidation state of the ferrocene groups were investigated. It was found that oxidation of the ferrocene moieties led to the release of RdFc. It was crucial to achieve precise control over the release of RdFc by applying the appropriate electrochemical signal, specifically, by applying the appropriate potential to the electrode. Importantly, the electrochemically controlled RdFc release process was performed at a temperature similar to that of the human body and monitored using a spectrofluorimetric technique. The presented system appears to be particularly suitable for transdermal delivery and delivery from intrabody implants.

Deciphering conformational changes in human serum albumin induced by bile salts using spectroscopic and molecular modeling approaches

Bile salts are physiologically-important natural amphiphilic biosurfactants synthesized in the liver and play a vital role in the solubilization and digestion of dietary lipids, cholesterol, and other fat-soluble compounds in the body. Bile salts also exhibit pharmacological and biological uses as carriers for transporting scarce water-soluble drugs and other chemicals owing to their unique emulsifying, solubilizing capacities and micelle forming ability. In this context, we present an endeavor towards the possibilities underlying the interaction and binding between the most abundant plasma protein namely, human serum albumin (HSA) and bile salts to demonstrate an intriguing interplay of hydrophobic, electrostatic and hydrogen bonding effects using steady state absorption, fluorescence emission, anisotropy, time-resolved emission, and molecular modelling approaches. The outcome illuminates how amphiphilic interfaces of bile salts under various physico-chemical conditions trigger the conformational changes and binding affinities of native and molten-globule forms of HSA. To elucidate non-covalent interactions during HSA-bile salt supramolecular host–guest complex formation, changes in intrinsic (tryptophan) and extrinsic (ANS) fluorescence have been investigated. The results reveal upon binding of bile salts in subdomain IIA of HSA, the protein undergoes conformational changes mediated primarily by hydrophobic interactions. Furthermore, time-resolved fluorescence measurements provide important structural and dynamical insights into the protein-bile salt supramolecular complexes. Additionally, molecular docking studies on these complexes clearly reveal spontaneous binding of bile salts into subdomain IIA of HSA while suggesting that the binding affinity decreases with the decreasing order of hydrophobicity of the bile salts (NaDC > NaC > NaTC) (ΔGdock = −29.64 kJ mol−1, −26.15 kJ mol−1, −14.35 kJ mol−1), respectively. This study exclusively highlights the molecular mechanism of conformational perturbation in the native (pH 7) and molten-globule (pH 3) forms of HSA, induced by bile salts. We believe that the results reported herein will be helpful in the design and formulation of protein-bile salt-based pharmacological carriers suitable for drug delivery.

Interfacial Rheological and Emulsion Properties of Self-Assembled Cyclodextrin-Oil Inclusion Complexes.

To investigate the effect of the molecular size of alkanes and the cavity size of cyclodextrins (CDs) on the formation of interfacial host-guest inclusion complexes, the interfacial tension (IFT) of CD (α-CD, β-CD, γ-CD) solutions against oils (hexadecane, dodecylbenzene) was determined by interfacial dilational rheology measurements. The results show that the "space compatibility" between CDs and oil molecules is crucial for the formation of interface host-guest inclusion complexes. Hexadecane with a smaller molecular size can form host-guest inclusion complexes with small cavities of α-CD and β-CD, dodecylbenzene with a larger molecular size can form interfacial aggregates with the medium-sized cavity of β-CD easily, and the polycyclic aromatic hydrocarbon molecules in kerosene can form inclusion complexes with the large cavity of γ-CD. The formation of interfacial inclusion complexes leads to lower IFT values, higher interfacial dilational modulus, nonlinear IFT responses to the interface area oscillating, and skin-like films at the oil-water interface. What's more, the phase behavior of Pickering emulsions formed by CDs with different oils is explored, and the phenomena in alkane-CD emulsions are in line with the results in dilatation rheology. The interfacial active host-guest structure in the kerosene-γ-CD system improves the stability of the Pickering emulsion, which results in smaller emulsion droplets. This unique space compatibility characteristic is of great significance for the application of CDs in selective host-guest recognition, sensors, enhanced oil recovery, food industries, and local drug delivery.

Competitive formation of molecular inclusion complexes of chlordecone and β-hexachlorocyclohexane with natural cyclodextrins: DFT and molecular dynamics study.

Chlordecone (CLD) and β-hexachlorocyclohexane (β-HCH) are chlorinated pesticides that coexist as persistent organic pollutants in the groundwater of several countries in the Caribbean, being an environmental issue. This work evaluates theoretically the competitive formation of host-guest complexes pesticides@cyclodextrines (CDs) as an alternative for water purification and selective separation of pesticides. Quantum mechanical calculations based on density functional theory (DFT) and classical molecular dynamics (MD) simulations were used to achieve information on geometries, energies, structure, and dynamics of guest-host complexes in the gas phase, implicit solvent medium, and in aqueous solutions. DFT studies showed that interactions of both pesticides with CDs are mediated by steric factors and guided by maximization of the hydrophobic interactions either with the other pesticide or with the CD cavity's inner atoms. MD results corroborate the formation of stable complexes of both pesticides with the studied CDs. α-CD exhibited a preference for the smaller β-HCH molecule over the CLD that could not perturb the formed complex. The simulation of competitive formation with γ-CD illustrated that this molecule could accommodate both pesticides inside its cavity. These results suggest that CDs with smaller cavity sizes such as α-CD could be used for selective separation of β-HCH from CLD in water bodies, while γ-CD could be used for methods that aim to remove both pesticides at the same time.

Charge Inversion Ion/Ion Reactions Coupled to Ion Mobility/Mass Spectrometry: Oligosaccharides.

Various ion mobility-based separation techniques and instruments have been recently developed to increase the operational resolution of ion mobility separations, especially of isomers and isobars. In addition to developments in instrumentation, different covalent and noncovalent derivatization techniques have helped achieve effective separations by magnifying minor differences in collision cross section. Among these methodologies is host-guest complex formation and, a new development presented herein, charge inversion ion-ion reactions coupled to ion mobility separations. We used these methods to enable formation of complexes between isomeric deprotonated oligosaccharides and alkaline earth metals (in solution) and alkaline earth metal-trisphenanthroline complexes (in vacuo), observing minor shifts in ion mobility arrival times for the charge inversion reaction products as well as unique mobility fingerprints indicative of separations of α/β anomers of disaccharides. For example, we have demonstrated separations between reducing disaccharides such as lactose and lactulose and nonreducing disaccharides. We also observed separations based on the pyranose/furanose configurations of the isomers. These results suggest the potential for ion/ion reactions to enable isomer separation of biomolecules from various compound classes using ion mobility-mass spectrometry (IM-MS).

A Microbial Community Cultured in Gradient Hydrogel for Investigating Gut Microbiome-Drug Interaction and Guiding Therapeutic Decisions.

Despite the recognition that the gut microbiota acts a clinically significant role in cancer chemotherapy, both mechanistic understanding and translational research are still limited. Maximizing drug efficacy requires an in-depth understanding of how the microbiota contributes to therapeutic responses, while microbiota modulation is hindered by the complexity of the human body. To address this issue, a 3D experimental model named engineered microbiota (EM) is reported for bridging microbiota-drug interaction research and therapeutic decision-making. EM can be manipulated in vitro and faithfully recapitulate the human gut microbiota at the genus/species level while allowing co-culture with cells, organoids, and isolated tissues for testing drug responses. Examination of various clinical and experimental drugs by EM reveales that the gut microbiota affects drug efficacy through three pathways: immunological effects, bioaccumulation, and drug metabolism. Guided by discovered mechanisms, custom-tailored strategies are adopted to maximize the therapeutic efficacy of drugs on orthotopic tumor models with patient-derived gut microbiota. These strategies include immune synergy, nanoparticle encapsulation, and host-guest complex formation, respectively. Given the important role of the gut microbiota in influencing drug efficacy, EM will likely become an indispensable tool to guide drug translation and clinical decision-making.

Inclusion Complex Formation with Tetra-PEGylated Tetraphenylporphyrin and Face-to-Face Cyclodextrin Dimer through Unprecedented Molecular Threading.

Herein, a host-guest inclusion complex formation between tetra-PEGylated tetraphenylporphyrin with a per-O-methylated cyclodextrin (CD) dimer through the molecular threading process that is physically unexpected to occur is described. Although the molecular size of the PEGylated porphyrin is much greater than that of the CD dimer, the sandwich-type porphyrin/CD dimer 1 : 1 inclusion complex was spontaneously formed in water. The ferrous porphyrin complex binds O2 reversibly in aqueous solution, which functions as an artificial O2 carrier in vivo. Pharmacokinetic study using rats revealed that the inclusion complex showed a long circulation in blood in contrast to the complex without PEG. We further demonstrate the unique host-guest exchange reaction from the PEGylated porphyrin/CD monomer 1/2 inclusion complex to the 1/1 complex with the CD dimer through the complete dissociation process of the CD monomers.

Comprehensive characterisation of the flurbiprofen/β-cyclodextrin inclusion complex using X-ray techniques and NMR spectroscopy

A new pharmaceutical form of a nonsteroidal anti-inflammatory drug complex composed of racemic flurbiprofen (FP) with a macrocyclic compound, forming a guest-host complex, was investigated. As with the other propionic acid compound, ketoprofen, three methods (co-precipitation, evaporation and heating-under-reflux) were used to prepare the β-cyclodextrin (β-CD) complex with FP. 1HNMR and X-ray powder diffraction (XRPD) in solution and solid state, respectively, were used to monitor the guest-host interactions. Only the heating-under-reflux method turned out to be suitable for host-guest complex formation. For the prospective method, a complex was prepared in the form of a crystalline powder, which was used as a starting material for the preparation of monocrystals suitable for X-ray crystallographic studies. The selected crystal was used to collect the diffraction data, which enabled the crystal and the molecular structure of the complex to be solved. This work is a connecting element in understanding the complete view of the interaction of FP with β-CD, mainly due to the results obtained with the X-ray single-crystal diffraction technique.

Aqueous solubilization of hydrophobic compounds by inorganic nano-ions: An unconventional mechanism

HypothesisSolubilization of hydrophobic compounds in water is commonly performed by using organic solubilizers such as hydrotropes, surfactants, co-solvents, and macrocycles to form host–guest complexes. 3,3′-commo-bis[closo-1,2-dicarba-3-cobaltadodecaborane] derivatives (COSANs) are fully inorganic and non-amphiphilic ionic boron clusters with nanometric size (nano-ions) showing superchaotropic properties as they strongly bind to neutral organic molecules. Therefore, we expect COSANs to act as solubilizers of sparingly water-soluble molecules, but with a mechanism different from all other organic solubilizers known so far. ExperimentsThe aqueous solubilization efficiency of COSANs towards butanol was evaluated by determining phase diagrams and comparing them to classical solubilizers. Nanostructuration of the mixture was studied using UV spectroscopy, small-angle X-ray, and neutron scattering with contrast variation. FindingsCOSANs act as efficient aqueous solubilizers of medium-chain alcohols (0.6 < log P < 1.5). Unlike surfactants, COSAN is an efficient solubilizer in its monomeric state, at concentrations well below its critical aggregation concentration. Solubilization by COSAN takes place with a bi-dimensional anisotropic growth of COSAN/butanol co-assemblies, whereas solubilization by surfactant occurs via an isotropic swelling of micelles. Appealingly, COSANs/2-butanol co-assemblies efficiently solubilize more hydrophobic compounds with log P values up to around 6, offering new opportunities in many applied fields.

Investigating the Solvent Effects on Binding Affinity of PAHs-ExBox4+ Complexes: An Alchemical Approach.

Polycyclic aromatic hydrocarbons (PAHs) are polluting agents, produced naturally or artificially, widely dispersed in the environment and potentially carcinogenic and immunotoxic to humans and animals, mainly for marine life. Recently, a tetracationic box-shaped cyclophane (ExBox4+) was synthesized, fully characterized, and revealed to form host-guest complexes with PAHs in acetonitrile, demonstrating the potential ability for it to act as a PAHs scavenger. This work investigates, through Molecular Dynamics (MD) simulations, the binding affinity between different PAHs and ExBox4+ in different solvents: chloroform (nonpolar), acetonitrile (polar protic), and water (polar protic). An alchemical method of simultaneous decoupling-recoupling (SDR) was used and implemented in a newly developed Python program called GHOAT, which fully automates the calculation of binding free energies and invokes the AMBER 2020 simulation package. The results showed that the affinity between ExBox4+ and PAHs in water is much larger than in organic media, with free energies between -5 and -20 kcal/mol, being able to act as a PHAs scavenger with great potential for applications in environmental chemistry such as soil washing. The results also reveal a significant correlation with the experimental available ΔG values. The methodology employed presents itself as an important tool for the in silico determination of binding affinities, not only available for charged cyclophanes but also extensible to several other HG supramolecular systems in condensed media, aiding in the rational design of host-guest systems in a significant way.

A novel inclusion complex of oxybenzone with C-methylresorcin[4]arene deters skin permeation.

Oxybenzone (OXB), a very widely used sunscreen ingredient has the potential to block both UVA and UVB but can penetrate through skin. Studies have revealed its presence in the blood and urine of most humans, which may lead to long-term health effects. As the confined cavities of macrocycles can alter the physical and chemical properties of encapsulated guests, in this study, we investigated the formation of host-guest complexes between C-methylresorcin[4]arene and OXB. Combined experimental (NMR spectroscopy, UV/vis absorption, and fluorescence spectroscopy) and theoretical investigation confirmed the formation of a weak host-guest complex that had a 1 : 1 stoichiometry. Furthermore, skin permeation testing revealed that complexation by C-methylresorcin[4]arene significantly reduced the skin permeation of OXB which can potentially limit the harmful effects of this organic sunscreen.