Nanoemulsions are a promising alternative for essential oil incorporation into active coatings. The influence of the preparation steps order on nanoemulsions\' physical properties is still little explored. This study aimed to analyze the effect of the sequence of preparation steps and of the oil and polymer concentration on the stability, physical properties, and antifungal activity of alginate-based cinnamon essential oil nanoemulsions. The nanoemulsions were produced by two strategies: (I) preparation directly into an alginate solution (Ultra-Turrax at 10,000 rpm for 5 min + Ultrasound 150 W for 3 min); and (II) preparation in water (Ultra-Turrax at 10,000 rpm for 5 min + Ultrasound 150 W for 3 min) followed by homogenization with a sodium alginate solution (Ultra-Turrax at 10,000 rpm for 1, 3 or 5 min). The nanoemulsion prepared by the second strategy showed better stability, physical properties, and antifungal activity. In general, the presence of alginate hindered the cavitation effects of ultrasound, leading to the increase of droplets size and consequently affecting emulsions stability, turbidity, and antifungal properties.

Previously, lipid nanoparticles (LDE) injected in women with endometriosis were shown to concentrate in the lesions. Here, the safety and feasibility of LDE carrying methotrexate (MTX) to treat deep infiltrating endometriosis was tested.
Prospective pilot study.
Perola Byington Hospital Reference for Women\'s Health.
Eleven volunteers (aged 30-47 years, BMI 26.15 ± 6.50 kg/m2) with endometriosis with visual analog scale pelvic pain scores (VAS) > 7 and rectosigmoid lesions were enrolled in the study.
Three patients were treated with LDE-MTX at single intravenous 25 mg/m2 dose of MTX and eight patients with two 25 mg/m2 doses with 1-week interval.
Clinical complaints, blood count, and biochemistry were analyzed before treatment and on days 90, 120, and 180 after LDE-MTX administration. Endometriotic lesions were evaluated by pelvic and transvaginal ultrasound (TVUS) before treatment and on days 30 and 180 after LDE-MTX administration.
No clinical complaints related with LDE-MTX treatment were reported by the patients, and no hematologic, renal, or hepatic toxicities were observed in the laboratorial exams. FSH, LH, TSH, free T4, anti-Müllerian hormone, and prolactin levels were also within normal ranges during the observation period. Scores for deep dyspareunia (p < 0.001), chronic pelvic pain (p = 0.008), and dyschezia (p = 0.025) were improved over the 180-day observation period. There was a non-significant trend for reduction of VAS scores for dysmenorrhea. Bowel lesions by TVUS were unchanged. No clear differences between the two dose levels in therapeutic responses were observed.
Results support the safety and feasibility of using LDE-MTX in women with deep infiltrating endometriosis as a novel and promising therapy for the disease. More prolonged treatment schemes should be tested in future placebo-controlled studies aiming to establish the usefulness of this novel nanomedicine approach.

Essential oil (EO) nanoemulsions have been recently studied due to their antimicrobial properties. Nevertheless, little is known about their possible negative effect against human gut microorganisms during their passage though the gastrointestinal tract. This work studied the effect of digestible (corn oil) or non-digestible (paraffin oil) citral nanoemulsions against specific microorganisms of human microflora under in vitro digestion conditions. The use of a citral lipid carrier (paraffin oil or corn oil) decreased the nanoemulsion particle size and increased its stability after gastric conditions with regards to the pure citral nanoemulsions. Digestible nanoemulsions formulated with corn oil and citral presented a lower bactericidal activity against Lactobacillus acidophilus and Escherichia coli after being subjected to in vitro digestion conditions in comparison to the initial nanoemulsion. However, a non-digestible nanoemulsion formulated with paraffin oil and citral presented a similar antimicrobial activity against L. acidophilus and E. coli to the one of the initial nanoemulsion. This evidences that non-digestible nanoemulsions may entrap the citral in the lipid core and thus retaining its antimicrobial potential during their passage though the gastrointestinal tract. Hence, this work evidences the impact of the lipid carrier digestibility when formulating antimicrobial nanoemulsions on certain intestinal probiotic bacteria.

Carvacrol is studied in different fields due to its microbial and antioxidant properties. Its use is limited because of the water insolubility and its strong taste. To overcome these problems, carvacrol has been successfully loaded into nanoemulsions. The low-energy emulsification method Phase Inversion Composition (PIC) is used to prepare oil-in-water nanoemulsions in the carvacrol/medium chain triglycerides (MCT)-(oleic acid-potassium oleate/Tween 80 ®)-water system. Oleic acid acts as a co-surfactant when it is neutralized with KOH along the emulsification path changing the spontaneous curvature of the interface when increasing the HLB number from 1 for the oleic acid to 20 for the potassium oleate and, therefore, changing the HLB number of the surfactant mixture. The phases diagrams are studied in order to understand the behaviour of the system and to establish the composition range where nanoemulsions can be obtained. Nanoemulsions are formed when the emulsification path crosses a region of direct or planar structure without excess of oil. Experimental design is performed in order to study the influence of composition variables as carvacrol/MCT ratio and (oleic-oleate)/Tween 80 ® ratio (OL-OT/T80 ratio) on the diameter of the nanoemulsions and their stability. It has been observed the importance of the HLB number of the surfactants mixture in order to obtain small-sized stable nanoemulsions. Surface response graphic shows that (OL-OT)/T80 ratio is a significant parameter in the mean diameter of the nanoemulsions. A minimum diameter is obtained for a (OL-OT)/T80 ratio 45/55 due to the fact that ratio is near the preferred HLB of the oil mixture and the emulsification path contains a wide liquid crystal monophasic region with all the oil incorporated in the structure. Diameters of 19 nm for carvacrol/MCT ratio of 30/70 or diameters of 30 nm for ratios of 45/55 with high stability values presented a good potential to be incorporated into edible films in the future. Regarding nanoemulsions stability an optimum value is also observed for a carvacrol/MCT ratio. The addition of another carrier oil as olive oil instead of MCT showed an improvement of the nanoemulsions stability against Ostwald ripening, probably due to the smaller solubility of olive oil. The use of olive oil does not significantly change the diameter of the nanoemulsion.

Intranasal administration offers an alternative and promising approach for direct nose-to-brain delivery. Herein, we developed two chitosan (CHT)-coated (and uncoated) nanoformulations of BNN27 (a synthetic C-17-spiro-dehydroepiandrosterone analogue), liposomes (LIPs), and nanoemulsions (NEs), and compared their properties and brain disposition (in vitro and in vivo). LIPs were formulated by thin film hydration and coated with CHT by dropwise addition. BNN27-loaded NEs (BNEs) were developed by spontaneous emulsification and optimized for stability and mucoadhesive properties. Mucoadhesive properties were evaluated by mucin adherence. Negatively charged CHT-coated LIPs (with 0.1% CHT/lipid) demonstrated the highest coating efficiency and mucoadhesion. BNEs containing 10% w/w Capmul-MCM and 0.3% w/w CHT demonstrated the optimal properties. Transport of LIP or NE-associated rhodamine-lipid across the blood-brain barrier (in vitro) was significantly higher for NEs compared to LIPs, and the CHT coating demonstrated a negative effect on transport. However, the CHT-coated BNEs demonstrated higher and faster in vivo brain disposition following intranasal administration compared to CHT-LIPs. For both BNEs and LIPs, CHT-coating resulted in the increased (in vivo) brain disposition of BNN27. Current results prove that CHT-coated NEs consisting of compatible nasal administration ingredients succeeded in to delivering more BNN27 to the brain (and faster) compared to the CHT-coated LIPs.

The influence of the carrier oil type on the bioavailability and bioactivity of flavonoids (quercetin, kaempferol, and apigenin) was examined using in vitro digestion, in situ intestinal perfusion, and pharmacokinetic studies. Here, medium-chain triglycerides (MCTs), long-chain triglycerides (LCTs), or MCT/LCT mixtures (1:1, w/w) served as the oil phase of excipient emulsions. Overall, the bioavailability and antioxidant activity of flavonoids increased when they were coingested with excipient emulsions. The in vitro bioaccessibility of flavonoids was affected by the carrier oil: LCT (17.9-22.8%) > MCT/LCT (12.1-13.7%) > MCT (9.2-12.6%). These differences were mainly attributed to the fact that the mixed micelles formed after the digestion of LCTs had larger hydrophobic domains to solubilize more flavonoids. However, in vivo pharmacokinetic experiments showed that the flavonoid concentrations in rat serum were comparable for all carrier oils (p > 0.05). Our results assist in formulating excipient emulsions to enhance the efficacy of flavonoids.

OBJECTIVE: Lipophilic cannabidiol can be solubilized in oil-in water nanoemulsions, which can then be impregnated into chitosan hydrogels forming another colloidal system that will facilitate cannabidiol\'s release. The delivery from both systems was compared, alongside structural and biological studies, to clarify the effect of the two carriers\' structure on the release and toxicity of the systems.
METHODS: Oil-in-water nanoemulsions (NEs) and the respective nanoemulsion-filled chitosan hydrogels (NE/HGs) were formulated as carriers of cannabidiol (CBD). Size, polydispersity and stability of the NEs were evaluated and then membrane dynamics, shape and structure of both systems were investigated with EPR spin probing, SAXS and microscopy. Biocompatibility of the colloidal delivery systems was evaluated through cytotoxicity tests over normal human skin fibroblasts. An ex vivo permeation protocol using porcine ear skin was implemented to assess the release of CBD and its penetration through the skin.
RESULTS: Incorporation of the NEs in chitosan hydrogels does not significantly affect their structural properties as evidenced through SAXS, EPR and confocal microscopy. These findings indicate the successful development of a novel nanocarrier that preserves the NE structure with the CBD remaining encapsulated in the oil core while providing new rheological properties advantageous over NEs. Moreover, NE/HGs proved to be more efficient as a carrier for the release of CBD. Cell viability assessment revealed high biocompatibility of the proposed colloids.

So far, various approaches have been proposed to improve dermal drug delivery. The use of chemical penetration enhancers has a long history of application, while methods based on the electrical current (such as iontophoresis) stand out as promising \"active\" techniques. Aiming to evaluate the contribution of different approaches to dermal delivery, in this work curcumin-loaded nanoemulsions with and without monoterpenes (eucalyptol or pinene) as chemical penetration enhancers, and a custom-made adhesive dermal delivery system based on iontophoresis were designed and assessed. In an in vivo study applying skin bioengineering techniques, their safety profile was proven. Three examined iontophoresis protocols, with total skin exposure time of 15 min (continuous flow for 15 min (15-0); 3 min of continuous flow and 2 min pause (3-2; 5 cycles) and 5 min of continuous flow and 1 min pause (5-1; 3 cycles) were equally efficient in terms of the total amount of curcumin that penetrated through the superficial skin layers (in vivo tape stripping) (Q3-2 = 7.04 ± 3.21 μg/cm2; Q5-1 = 6.66 ± 2.11 μg/cm2; Q15-0 = 6.96 ± 3.21 μg/cm2), significantly more efficient compared to the referent nanoemulsion and monoterpene-containing nanoemulsions. Further improvement of an efficient mobile adhesive system for iontophoresis would be a practical contribution in the field of dermal drug application.

In cancer therapy, stimulus-responsive drug delivery systems are of particular interest for reducing side effects in healthy tissues and improving drug selectivity in the tumoral ones. Here, a strategy for the preparation of a photo-responsive cross-linked trilayer deposited onto an oil-in-water nanoemulsion via a layer-by-layer technique is reported. The system is made of completely biocompatible materials such as soybean oil, egg lecithin and glycol chitosan, with heparin as the polymeric shell. The oil core is pre-loaded with curcumin as a model lipophilic active molecule with anti-tumoral properties. The trilayer cross-linkage is performed via a photoinitiator-free thiol-ene \'click\' reaction. In particular, the system is implemented with an o-nitrobenzyl group functionalized with a thiol moiety which can perform both the thiol-ene \'click\' reaction and the cleavage meant for controlled drug release at two different wavelengths, respectively. So the preparation and characterization of a photo-responsive natural nanocarrier (PNC) that is stable under physiological conditions owing to the thiol-ene cross-linkage are reported. PNC performance has been assessed in vitro on melanoma cells as well as in vivo on xenograft tumour-induced mice.

BACKGROUND: Chickpea protein isolate (CPI) originating from chickpeas has the advantages of facilitating the stability of food emulsions. Stevioside (STE) exhibits a notable surface activity and can improve the water solubility of numerous hydrophobic nutrients. STE and protein mixtures show great potential as emulsions stabilizers. The present study aimed to prepare a novel nanoemulsion for encapsulating lutein (LUT) by ultrasonic homogenization using chickpea protein isolate-stevioside complex (CPI-STE) as a stabilizer and also to investigate the physicochemical characteristics.
RESULTS: The results obtained showed that different preparation conditions demonstrated significant influences on the physicochemical properties of CPI-STE-LUT nanoemulsions. Under the optimal condition, the average particle size of CPI-STE-LUT nanoemulsions was 195.1 nm, and the emulsifying and encapsulation efficiencies of lutein were 91.04% and 87.56%, respectively. CPI-STE-LUT nanoemulsions stabilized by CPI-STE could significantly increase the emulsifying and encapsulation efficiencies of lutein compared to that stabilized by CPI. Fourier transform infrared spectroscopy revealed that hydrogen bond was the main binding force of CPI and lutein, and there was a covalent bond between the two molecules. Furthermore, the stability of CPI-STE-LUT nanoemulsions in gastrointestinal phase was higher than that of CPI-LUT nanoemulsions, which could load lutein more effectively and be more resistant to digestive enzymes.
CONCLUSIONS: The present study reports the physicochemical characterization of CPI-STE-LUT nanoemulsions for the first time. CPI-STE-LUT nanoemulsions were characterized by a small average particle size lower than 200 nm, as well as high emulsifying and encapsulation efficiencies, and good stability. © 2021 Society of Chemical Industry.