Compartmentalized CRISPR Reactions (CCR) for High-Throughput Screening of Guide RNA Potency and Specificity.

CRISPR ribonucleoproteins (RNPs) use a variable segment in their guide RNA (gRNA) called a spacer to determine the DNA sequence at which the effector protein will exhibit nuclease activity and generate target-specific genetic mutations. However, nuclease activity with different gRNAs can vary considerably in a spacer sequence-dependent manner that can be difficult to predict. While computational tools are helpful in predicting a CRISPR effector's activity and/or potential for off-target mutagenesis with different gRNAs, individual gRNAs must still be validated in vitro prior to their use. Here, the study presents compartmentalized CRISPR reactions (CCR) for screening large numbers of spacer/target/off-target combinations simultaneously in vitro for both CRISPR effector activity and specificity by confining the complete CRISPR reaction of gRNA transcription, RNP formation, and CRISPR target cleavage within individual water-in-oil microemulsions. With CCR, large numbers of the candidate gRNAs (output by computational design tools) can be immediately validated in parallel, and the study shows that CCR can be used to screen hundreds of thousands of extended gRNA (x-gRNAs) variants that can completely block cleavage at off-target sequences while maintaining high levels of on-target activity. It is expected that CCR can help to streamline the gRNA generation and validation processes for applications in biological and biomedical research.

Scope and Limitations of Using Microemulsions for the Covalent Patterning of Graphene.

Patterning of graphene (functionalizing some areas while leaving others intact) is challenging, as all the C atoms in the basal plane are identical, but it is also desirable for a variety of applications, like opening a bandgap in the electronic structure of graphene. Several methods have been reported to pattern graphene, but most of them are very technologically intensive. Recently, we reported the use of microemulsions as templates to pattern graphene at the µm scale. This method is very simple and in principle tunable, as emulsions of different droplet size and composition can be prepared easily. Here, we explore in detail the scope of this methodology by applying it to all the combinations of four different emulsions and three different organic reagents, and characterizing the resulting substrates exhaustively through Raman, SEM and AFM. We find that the method is general, works better when the reactive species are outside the micelles, and requires reactive species that involve short reaction times.

Rhodamine B for Probing the Effects of Modifications in Cetrimonium Bromide Counter-anions by Transition Metals on CTAB/Butanol/n-hexane/water Microemulsion.

Dye solubilization in microemulsion based on Cetyltrimethylammonium bromide (CTAB) and its modified forms (counter-anions based upon Zn2+, Cu2+ and Fe3+) is comparatively innovative and not explored in existing literature. Here, surfactant with modified counterions (SMCs) were used to study the effects of metal chlorides (ZnCl2, CuCl2 and FeCl3) modifications on the comparative solubilization of Rhodamine-B (RB) by Cetyltrimethylammonium bromide (CTAB) and its modified forms. The solubility of RB in different microemulsions were studied using UV-Visible spectroscopy and phase diagrams of CTAB with modified counter ions CTA+[ZnCl2.Br]- named as CZN-1, CTA+[CuCl2.Br]- named as CCU-1 and CTA+[FeCl3.Br]- named as CFE-1 based upon surfactant with modified counter ions (SMCs). Four different points in microemulsion region of phase diagram were selected with different percentage composition of Smix (surfactant and co-surfactant), oil and RB (taken as water component). The interaction of RB, CCU-1, CFE-1 and CZN-1 within microemulsion environment were studied using Fluorescence spectroscopy. Emission spectra of RB in CCU-1 and CFE-1 based microemulsion confirmed that RB formed complexes with Cu and Fe ions. It was also found that RB was less soluble in CTAB based microemulsion as compared to microemulsions based on SMCs. This novel research study will expose new path for future research work related to microemulsion.

Microemulsions strongly promoted the activity of α-bisabolol against different Leishmania species and its skin permeation.

This study aimed to develop microemulsions (MEs) containing α-bisabolol for the topical treatment of cutaneous leishmaniasis (CL). Initially, pseudoternary phase diagrams were developed using α-bisabolol as the oil phase, Eumulgin® CO 40 as the surfactant, Polymol® HE as the co-surfactant, and distilled water as the aqueous phase. Two transparent liquid systems (TLS) containing 5% of α-bisabolol were selected and characterized (F5E25 and F5EP25). Next, skin permeation and retention assays were performed using Franz cells. The interaction of the formulation with the stratum corneum (SC) was evaluated using the FTIR technique. The cytotoxicity was evaluated in murine peritoneal macrophages. Finally, the antileishmanial activity of microemulsions was determined in promastigotes and amastigotes of L. amazonensis (strain MHOM/BR/77/LTB 0016). As a result, the selected formulations showed isotropy, nanometric size (below 25 nm), Newtonian behavior and pH ranging from 6.5 to 6.9. The MEs achieved a 2.5-fold increase in the flux and skin-permeated amount of α-bisabolol. ATR-FTIR results showed that microemulsions promoted fluidization and extraction of lipids and proteins of the stratum corneum, increasing the diffusion coefficient and partition coefficient of the drug in the skin. Additionally, F5E25 and F5EP25 showed higher activity against promastigotes (IC50 13.27 and 18.29, respectively) compared to unencapsulated α-bisabolol (IC50 53.8). Furthermore, F5E25 and F5EP25 also showed antileishmanial activity against intracellular amastigotes of L. amazonensis, with IC50 50 times lower than free α-bisabolol and high selectivity index (up to 15). Therefore, the systems obtained are favorable to topical administration, with significant antileishmanial activity against L. amazonensis promastigotes and amastigotes, being a promising system for future in vivo trials.

Essential oil and Waste Hydrosol of Ocimum Tenuiflorum L.: A Low-Cost Raw Material Source of Eugenol, Botanical Pesticides, and Therapeutic Potentiality.

In this study, essential oils and waste hydrosols of leaves of Ocimum tenuiflorum in four different geographical locations were extracted by hydrodistillation method and using gas chromatography/mass spectrometry (GC/MS) for chemical composition analysis. All four essential oil samples contained the main components (E)-ß-caryophyllene (27.8-49.0 %), trans-ß-elemene (20.3-37.1 %) and eugenol (9.0-44.0 %). Three of the four hydrosol samples had eugenol in absolute content (94.5-98.6 %), while the remaining hydrosol sample had two main components, elemicin (77.8 %) and eugenol (14.2 %). Essential oils and hydrosols demonstrated larvicidal activities against four important disease-transmitting mosquito species including Aedes aegypti, Aedes albopictus, Culex quinquefasciatus, and Culex fuscocephala with 24-h LC50 values in the range 15.42-56.01 µg/mL and 53.88-97.80 µg/mL for the essential oils and the hydrosols, respectively. Essential oils and hydrosols strongly inhibited the acetylcholinesterase (AChE) enzyme of electric eels with IC50 values in the range of 25.35-107.19 µg/mL. Microemulsion (ME) can be considered as a sustainable pesticide formulation over 300 days and has improved larvicidal activity compared to free essential oil. The O. tenuiflorum in Vietnam can be considered a low-cost source of eugenol, botanical pesticides that control disease-transmitting mosquitoes, as well as having therapeutic potential to be further investigated.

Advancements in Characterization Techniques for Microemulsions: From Molecular Insights to Macroscopic Phenomena.

Microemulsions are thermodynamically stable, optically isotropic, transparent, or semi-transparent mixed solutions composed of two immiscible solvents stabilized by amphiphilic solutes. This comprehensive review explores state-of-the-art techniques for characterizing microemulsions, which are versatile solutions essential across various industries, such as pharmaceuticals, food, and petroleum. This article delves into spectroscopic methods, nuclear magnetic resonance, small-angle scattering, dynamic light scattering, conductometry, zeta potential analysis, cryo-electron microscopy, refractive index measurement, and differential scanning calorimetry, examining each technique's strengths, limitations, and potential applications. Emphasizing the necessity of a multi-technique approach for a thorough understanding, it underscores the importance of integrating diverse analytical methods to unravel microemulsion structures from molecular to macroscopic scales. This synthesis provides a roadmap for researchers and practitioners, fostering advancements in microemulsion science and its wide-ranging industrial applications.

Simplex Lattice Design and Machine Learning Methods for the Optimization of Novel Microemulsion Systems to Enhance p-Coumaric Acid Oral Bioavailability: In Vitro and In Vivo Studies.

Novel p-coumaric acid microemulsion systems were developed to circumvent its absorption and bioavailability challenges. Simplex-lattice mixture design and machine learning methods were employed for optimization. Two optimized formulations were characterized using in vitro re-dispersibility and cytotoxicity on various tumor cell lines (MCF-7, CaCO2, and HepG2). The in vivo bioavailability profiles of the drug loaded in the two microemulsion systems and in the suspension form were compared. The optimized microemulsions composed of Labrafil M1944 CS (5.67%)/Tween 80 (38.71%)/Labrasol (38.71%)/water (16.92%) and Capryol 90 (0.50%)/Transcutol P (26.67%)/Tween 80 (26.67%)/Labrasol (26.67%)/water (19.50%), respectively. They revealed uniform and stable p-coumaric acid-loaded microemulsion systems with a droplet size diameter of about 10 nm. The loaded microemulsion formulations enhanced the drug re-dispersibility in contrast to the drug suspension which exhibited 5 min lag time. The loaded formulae were significantly more cytotoxic on all cell lines by 11.98-16.56 folds on MCF-7 and CaCo2 cells and 47.82-98.79 folds on HepG2 cells higher than the pure drug. The optimized microemulsions were 1.5-1.8 times more bioavailable than the drug suspension. The developed p-coumaric acid microemulsion systems could be considered a successful remedy for diverse types of cancer.

An intravitreal-injectable hydrogel depot doped borneol-decorated dual-drug-coloaded microemulsions for long-lasting retina delivery and synergistic therapy of wAMD.

Sustained retina drug delivery and rational drug combination are considered essential for enhancing the efficacy of therapy for wet age-related macular degeneration (wAMD) due to the conservative structure of the posterior ocular segment and the multi-factorial pathological mechanism. Designing a drug co-delivery system that can simultaneously achieve deep penetration and long-lasting retention in the vitreous is highly desired, yet remains a huge challenge. In this study, we fabricated Bor/RB-M@TRG as an intravitreal-injectable hydrogel depot for deep penetration into the posterior ocular segment and long-lasting distribution in the retinal pigment epithelium (RPE) layer. The Bor/RB-M@TRG consisted of borneol-decorated rhein and baicalein-coloaded microemulsions (Bor/RB-M, the therapy entity) and a temperature-responsive hydrogel matrix (the intravitreal depot). Bor/RB-M exhibited the strongest in vitro anti-angiogenic effects among all the groups studied, which is potentially associated with improved cellular uptake, as well as the synergism of rhein and baicalein, acting via anti-angiogenic and anti-oxidative stress pathways, respectively. Importantly, a single intravitreal (IVT) injection with Bor/RB-M@TRG displayed significant inhibition against the CNV of wAMD model mice, compared to all other groups. Particularly, coumarin-6-labeled Bor/RB-M@TRG (Bor/C6-M@TRG) could not only deeply penetrate into the retina but also stably accumulate in the RPE layer for at least 14 days. Our design integrates the advantages of borneol-decorated microemulsions and hydrogel depots, offering a promising new approach for clinically-translatable retinal drug delivery and synergistic anti-wAMD treatment.

Separation of Palladium from Alkaline Cyanide Solutions through Microemulsion Extraction Using Imidazolium Ionic Liquids.

In this paper, three imidazolium-based ionic liquids, viz., 1-butyl-3-undecyl imidazolium bromide ([BUIm]Br), 1-butyl-3-octyl imidazolium bromide ([BOIm]Br), and 1-butyl-3-hexadecyl imidazolium bromide ([BCIm]Br), were synthesized. Three novel microemulsions systems were constructed and then were used to recover Pd (II) from cyanide media. Key extraction parameters such as the concentration of ionic liquids (ILs), equilibration time, phase ratio (RA/O), and pH were evaluated. The [BUIm]Br/n-heptane/n-pentanol/sodium chloride microemulsion system exhibited a higher extraction percentage of Pd (II) than the [BOIm]Br/n-heptane/n-pentanol/sodium chloride and [BCIm]Br/n-heptane/n-pentanol/sodium chloride microemulsion systems. Under the optimal conditions (equilibrium time of 10 min and pH 10), the extraction percentages of these metals were all higher than 98.5% when using the [BUIm]Br/n-heptane/n-pentanol/sodium chloride microemulsion system. Pd(CN)42- was separated through a two-step stripping procedure, in which Fe (III) and Co (III) were first separated using KCl solution, then Pd(CN)42- was stripped using KSCN solution (separation factors of Pd from Fe and Co exceeded 103). After five extraction-recovery experiments, the recovery of Pd (II) through the microemulsion system remained over 90%. The Pd (II) extraction mechanism of the ionic liquid [BUIm]Br was determined to occur via anion exchange, as shown by spectral analysis (UV, FTIR), Job's method, and DFT calculations. The proposed process has potential applications for the comprehensive treatment of cyanide metallurgical wastewater.

Assessment of antimicrobial activity of melittin encapsulated in bicontinuous microemulsions prepared using renewable oils.

The objective of this study is to demonstrate that melittin, a well-studied antimicrobial peptide (AMP), can be solubilized in an active form in bicontinuous microemulsions (BMEs) that employ biocompatible oils. The systems investigated consisted of Winsor-III and -IV BME phases composed of Water/Aerosol-OT (AOT)/Polysorbate 85/isopropyl myristate and a Winsor-IV BME employing Polysorbate 80 and limonene. We found that melittin resided in an α-helix-rich configuration and was in an apolar environment for the AOT/Polysorbate 85 Winsor-III system, suggesting that melittin interacted with the surfactant monolayer and was in an active conformation. An apolar environment was also detected for melittin in the two Winsor-IV systems, but to a lesser extent than the Winsor-III system. Small-angle X-ray scattering analysis indicated that melittin at a concentration of 1.0 g/Laq in the aqueous subphase of the Winsor-IV systems led to the greatest impact on the BME structure (e.g., decrease of quasi-periodic repeat distance and correlation length and induction of interfacial fluidity). The antimicrobial activity of the Polysorbate 80 Winsor-IV system was evaluated against several bacteria prominent in chronic wounds and surgical site infections (SSIs). Melittin-free BMEs inhibited the growth of all tested bacteria due to its oil, limonene, while the inclusion of 1.0 g/Laq of melittin in the BMEs enhanced the activity against several bacteria. A further increase of melittin concentration in the BMEs had no further enhancement. These results demonstrate the potential utility of BMEs as a delivery platform for AMPs and other hydrophilic and lipophilic drugs to inhibit antibiotic-resistant microorganisms in chronic wounds and SSIs.

Role of mucoadhesive agent in ocular delivery of ganciclovir microemulsion: cytotoxicity evaluation in vitro and ex vivo.

PURPOSE: The aim of the present study was to investigate increase in delivery of drug upon formulation as mucoadhesive microemulsion system and further to investigate possibility of any cytotoxic effects using such formulation. MATERIAL AND METHODS: Considering hydrophilic and small molecular nature of the drug, it was attempted to be formulated as microemulsion, by using pseudo ternary phase diagram method. Thus, three types of microemulsions were prepared; oil in water, water in oil type and chitosan-coated microemulsion. These microemulsions were characterized for several physicochemical properties like size, zeta potential, Polydispersity index, and compared for in vitro cell viability and ex vivo corneal irritation study. RESULTS: All three microemulsions were quite stable, transparent and homogenous systems. They showed similar drug release pattern, but highest ex vivo goat corneal permeation was observed with Chitosan coated microemulsion when compared with ganciclovir solution. CONCLUSION: All microemulsions were found to be non-irritant in in vitro cell viability assay and ex vivo corneal irritation study, indicating the potential of using such systems for delivery of drug to eye.

Essential Oil Microemulsions Inactivate Antibiotic-Resistant Bacteria on Iceberg Lettuce during 28-Day Storage at 4 °C.

The objective of this study was to investigate the antimicrobial activities of essential oil-based microemulsions in the wash water against Escherichia coli O157:H7 and Pseudomonas fluorescens on Iceberg lettuce. Evaluated wash microemulsions included oregano oil, lemongrass oil, and cinnamon oil, along with a plant-based emulsifier for improved solubility. Iceberg lettuce was inoculated for 2 min with E. coli O157:H7 (6.0 log CFU/g) or P. fluorescens (6.0 log CFU/g) and then dip-treated in a phosphate buffered saline (PBS) control, 50 ppm chlorine, 3% hydrogen peroxide treatment or a 0.1%, 0.3%, or 0.5% microemulsion solution. Treated leaves were stored at 4 °C, and analyzed for surviving bacteria on days 0, 3, 7, 10, 14, 21, and 28. Efficacies of the antimicrobials were concentration and storage-time dependent. There was a 1.26−4.86 log CFU/g reduction in E. coli O157:H7 and significant reductions (0.32−2.35 log CFU/g) in P. fluorescens during storage at days 0−28 (p < 0.05). The 0.1% oregano oil microemulsion resulted in the best visual appeal in Iceberg leaves inoculated with E. coli O157:H7 and showed better improvement in the quality of the Iceberg leaves inoculated with spoilage bacteria P. fluorescens. The results suggest that 0.5% cinnamon and 0.3% oregano oil treatments have the potential to provide natural, eco-friendly, and effective alternatives to chemicals for the decontamination of leafy greens, eliminating E. coli O157:H7 and P. fluorescens.

Interplay of Polarity and Confinement in Asymmetric Catalysis with Chiral Rh Diene Complexes in Microemulsions.

Microemulsions provide a unique opportunity to tailor the polarity and liquid confinement in asymmetric catalysis via nanoscale polar and nonpolar domains separated by a surfactant film. For chiral diene Rh complexes, the influence of counterion and surfactant film on the catalytic activity and enantioselectivity remained elusive. To explore this issue chiral norbornadiene Rh(X) complexes (X=OTf, OTs, OAc, PO2 F2 ) were synthesized and characterized by X-ray crystallography and theoretical calculations. These complexes were used in Rh-catalyzed 1,2-additions of phenylboroxine to N-tosylimine in microemulsions stabilized either exclusively by n-octyl-ß-D-glucopyranoside (C8 G1 ) or a C8 G1 -film doped with anionic or cationic surfactants (AOT, SDS and DTAB). The Rh(OAc) complex showed the largest dependence on the composition of the microemulsion, yielding up to 59 % (90 %ee) for the surfactant film doped with 5 wt% of AOT as compared to 52 % (58 %ee) for neat C8 G1 at constant surfactant concentration. Larger domains, determined by SAXS analysis, enabled further increase in yield and selectivity while the reaction rate almost remained constant according to kinetic studies.

Restoration of paper artworks with microemulsions confined in hydrogels for safe and efficient removal of adhesive tapes.

The presence of pressure-sensitive tapes (PSTs) on paper artworks, either fortuitous or specifically applied for conservation purposes, is one of the most frequent and difficult issues encountered during restoration. Aged PSTs can damage or disfigure artworks, compromising structural integrity, readability, and enjoyment. Current procedures are often inherently hazardous for artistic media and paper support. Challenged by the necessity to remove PSTs from a contemporary and an ancient drawing (20th century, by artists da Silva and Hayter, and a 16th-century drawing of one figure from the Sistine Chapel by Michelangelo), we addressed this issue from a physicochemical perspective, leveraging colloid and interface science. After a characterization of the specific PSTs present on the artifact, we selected a highly water-retentive hydrogel as the host of 23% wt/wt of "green" organic solvents uniformly dispersed within the gel in the form of nanosized droplets. The double confinement of the organic solvent in the nanodroplets and into the gel network promotes a tailored, controlled removal of PSTs of different natures, with virtually no interaction with the solvent-sensitive artwork. This noninvasive procedure allows complete retrieval of artwork readability. For instance, in the ancient drawing, the PST totally concealed the inscription, "di mano di Michelangelo" ("from Michelangelo's hand"), a possibly false attribution hidden by a collector, which is now perfectly visible and whose origin is currently under investigation. Remarkably, the same methodology was successful for the removal of aged PST adhesive penetrated inside paper fibers of a drawing from the celebrated artist Lucio Fontana.

Improvement of the Solubilization and Extraction of Curcumin in an Edible Ternary Solvent Mixture.

A water-free, ternary solvent mixture consisting of a natural deep eutectic solvent (NADES), ethanol, and triacetin was investigated concerning its ability to dissolve and extract curcumin from Curcuma longa L. To this purpose, 11 NADES based on choline chloride, acetylcholine, and proline were screened using UV-vis measurements. A ternary phase diagram with a particularly promising NADES, based on choline chloride and levulinic acid was recorded and the solubility domains of the monophasic region were examined and correlated with the system's structuring via light scattering experiments. At the optimum composition, close to the critical point, the solubility of curcumin could be enhanced by a factor of >1.5 with respect to acetone. In extraction experiments, conducted at the points of highest solubility and evaluated via HPLC, a total yield of ~84% curcuminoids per rhizome could be reached. Through multiple extraction cycles, reusing the extraction solvent, an enrichment of curcuminoids could be achieved while altering the solution. When counteracting the solvent change, even higher concentrated extracts can be obtained.

Advanced Materials in Cultural Heritage Conservation.

Cultural Heritage is a crucial socioeconomic resource; yet, recurring degradation processes endanger its preservation. Serendipitous approaches in restoration practice need to be replaced by systematically addressing conservation issues through the development of advanced materials for the preservation of the artifacts. In the last few decades, materials and colloid science have provided valid solutions to counteract degradation, and we report here the main highlights in the formulation and application of materials and methodologies for the cleaning, protection and consolidation of works of art. Several types of artifacts are addressed, from murals to canvas paintings, metal objects, and paper artworks, comprising both classic and modern/contemporary art. Systems, such as nanoparticles, gels, nanostructured cleaning fluids, composites, and other functional materials, are reviewed. Future perspectives are also commented, outlining open issues and trends in this challenging and exciting field.

Ocular microemulsion of brinzolamide: Formulation, physicochemical characterization, and in vitro irritation studies based on EpiOcular™ eye irritation assay.

In recent years, the hydrophobic active substances have led researchers to develop new formulations to enhance bioavailability and dissolution rate; brinzolamide, a lipophilic drug belongs to carbonic anhydrase inhibitors, which cause reduction of intraocular pressure in patients suffering from glaucoma. Currently, the marketed product of brinzolamide is in the form of ocular drops; nonetheless, the conventional drops provide decreased therapeutic efficacy owing to their low bioavailability and pulsed drug release. Thus, the development of novel ocular formulations such as topical microemulsions is of high importance. In this work, the preparation of new microemulsions containing brinzolamide (0.2, 0.5 and 1% w/w) and comprised from isopropyl myristate, tween 80 and span 20 and Cremophor EL was performed. The obtained microemulsions were further characterized for their physicochemical properties. In addition, Fourier Transformed-Infrared spectroscopy was used touate the compatibility of active ingredients and components. In vitro release studies along with kinetic modeling were performed using the dialysis membrane method in simulated tear fluid. Bioadhesion studies were performed using Texture analysis. Finally, in vitro ocular irritation based on EpiOcular™ Eye Irritation Test and cytocompatibility studies was performed to examine any possible harm on ocular cells and predict in vivo safety profile.

Insightful exploring of advanced nanocarriers for the topical/transdermal treatment of skin diseases.

Dermatological products constitute a big segment of the pharmaceutical market. From conventional products to more advanced ones, a wide variety of dosage forms have been developed till current date. A representative of the advanced delivery means is carrier-based systems, which can load large number of drugs for treatment of dermatological diseases, or simply for cosmeceutical purposes. To make them more favorable for topical delivery, further incorporation of these carriers in a topical vehicle, such as gels or creams is made. Therefore in this review article, an overview is compiled of the most commonly encountered novel carrier based topical delivery systems; namely lipid based (nanoemulsions, microemulsions, solid lipid nanoparticles [SLNs] and nanostructured lipid carriers [NLCs]), and vesicular carriers (non-deformable, such as liposomes, niosomes, emulsomes and cerosomes, and deformable, such as transfersomes, ethosomes, transethosomes, and penetration enhancer vesicles), with special emphasis on those loaded in a secondary gel vehicle. A special focus was made on the commonly encountered dermatological diseases, such as bacterial and fungal infections, psoriasis, dermatitis, eczema, vitiligo, oxidative damage, aging, alopecia, and skin cancer.

Development and Evaluation of Topical Delivery of Microemulsions Containing Adapalene (MEs-Ap) for Acne.

The main objective of the study was to prepare the microemulsions containing adapalene (MEs-Ap) to enhance epidermal penetration, dermal retention, and local bioavailability compared with the commercial preparation. The optimal formulations were selected by solubility experiments, pseudo-ternary phase diagram, and percutaneous permeation experiments and the physiochemical properties were also investigated. Then, the study of permeability, retention, safety, pharmacodynamics, and pharmacokinetics in the skin for MEs-Ap compared with the commercial preparation were researched. The optimized formulation was developed as follows: the ratio of AP, isopropyl myristate, polyoxyethylene hydrogenated castor oil, ethanol, and water was 0.01:1:1.25:3.75:4 (w/w). The globule size and average viscosity of the optimized MEs-Ap were 99.34 nm and 1.7 mPa·s, respectively, which was oil-in-water microemulsion without serious irritation or allergy for skin. The Js, Qn, and Qretention of MEs-Ap (0.81 ± 0.19 µg/cm2/h, 24.73 ± 4.24 µg/cm2, 2.08 ± 0.18 µg/cm2) were apparently higher than Differin® (0.022 ± 0.009 µg/cm2/h, 0.536 ± 0.103 µg/cm2, and 0.523 ± 0.130 µg/cm2) respectively. The local bioavailability study showed that the AUC0 → 36h of the MEs-Ap in the dermal (19.6 ± 1.22 µg/cm2) was significantly improved comparing to Differin® (13.9 ± 1.73 µg/cm2) (p < 0.01). The pharmacodynamics study showed that the therapeutic effect of MEs-Ap was better than that of Differin® in the acne model of rabbit auricle. These results suggested that the MEs-Ap could be considered as a having higher epidermal penetrability, dermal retention, local bioavailability, efficacy, and safety topical preparations for acne. Graphical abstract.

Vitamin C: One compound, several uses. Advances for delivery, efficiency and stability.

Vitamin C (Vit C) is a potent antioxidant with several applications in the cosmetic and pharmaceutical fields. However, the biggest challenge in the utilization of Vit C is to maintain its stability and improve its delivery to the active site. Several strategies have been developed such as: controlling the oxygen levels during formulation and storage, low pH, reduction of water content in the formulation and the addition of preservative agents. Additionally, the utilization of derivatives of Vit C and the development of micro and nanoencapsulated delivery systems have been highlighted. In this article, the multiple applications and mechanisms of action of vitamin C will be reviewed and discussed, as well as the new possibilities of delivery and improvement of stability.