Nanoemulsion Delivery System Research Articles

Effect of salt ions on an ultrasonically modified soybean lipophilic protein nanoemulsion

SummarySoybean lipophilic proteins (LP) are promising emulsifiers for nanoemulsion delivery systems. We analysed the effect of common salt ions on the stability of nanoemulsion delivery systems that contained ultrasonically modified soybean LP. Moreover, explored the mechanism of influence. The LP nanoemulsions presented large absolute zeta (ζ) potentials at low salt ion concentrations, and their particle size distribution was relatively uniform. The emulsification, encapsulation efficiency and oxidation stability were superior to those of other nanoemulsions. The ultrasonically modified samples presented higher absolute ζ potentials and smaller droplet sizes than the pristine ones and formed uniform protein films at different salt ion concentrations. Therefore, ultrasonication improved the emulsification, encapsulation efficiency and oxidation stability of the emulsions, effectively improve the stability of nano‐delivery systems in different salt ion environments and maximise delivery efficiency at low salt ion concentrations. These results are helpful for the development of LP nanoemulsion systems that are stable at different salt ion concentrations.

An in vitro approach to study the absorption of a new oral formulation of berberine

BackgroundBerberine (BBR) possesses several biological activities in humans, but the poor water solubility and low oral bioavailability preclude its pharmacological use. To overcome these limitations, several formulations have been prepared including encapsulation, micro- and nano-emulsion. The aim of this study was to develop a nanoemulsion delivery system of BBR and to evaluate its membrane permeability using Caco-2 cell model. MethodsNanoemulsions containing different ratios BBR:Compritol ATO 888 (a lipid excipient) were formulated at 25 and 80 °C. The controls consisted of BBR and carboxymethylcellulose. Absorption of BBR nanoemulsions delivery systems was evaluated in vitro by using human colon adenocarcinoma cells (Caco-2) Transwell model. The amount of permeated BBR was determined by LC-HR-MS at time zero and every 30 min for 180 min. ResultsNanoemulsions significantly improved apical-to-basal transport of BBR compared to the control formulation. Kinetics of BBR uptake showed that the maximum amount absorbed was reached after 90−120 min and the percentage of BBR absorbed by Caco-2 cells increased with increasing BBR-to-Compritol ratio (1:20 > 1:10 > 1:5 > 1:1). Moreover, the formulation prepared at 80 °C showed a higher absorption rate (6-fold increment compared to control) than that developed at 25 °C (4.5-fold increment compared to control). Furthermore, demethyl-BBR was detected after 120 min of incubation as partial metabolism of berberine in the intestine. ConclusionsOverall, in our in vitro model, these new nanoemulsions seem to potentially improve the absorption of BBR. However, in vivo studies are required in order to demonstrate the bioavailability of BBR from this new formulation.

Physical Stability, Oxidative Stability, and Bioactivity of Nanoemulsion Delivery Systems Incorporating Lipophilic Ingredients: Impact of Oil Saturation Degree.

There is great interest in the application of a lipid-based delivery system (like nanoemulsion) to improve the bioavailability of lipophilic components. Although emulsion characteristics are believed to be influenced by oil types, there is still a lack of systematic research concentrating on the effect of oil saturation degree on the nanoemulsion quality, especially for evaluation of the bioactivity. Here, we aimed to test the effect of oil saturation degree on the physical stability, oxidative stability, and bioactivity of the designed nanoemulision system. Our findings suggest that the oxidative stability and bioactivity of a nanoemulsion incorporating tocopherol and sesamol highly depend on the oil saturation. A nanoemulsion with an oil with a high degree of unsaturation was more susceptible to oxidation, and addition of tocopherol and sesamol could retard the lipid oxidation. Sesamol exhibited better bioactivity during the experiment compared with tocopherol in the Caenorhabditis elegans (C. elegans) model. The lipid-lowering effect of tocopherol and sesamol increased with lower saturation oil groups. The antioxidant activity of tocopherol and sesamol was higher in the high saturation oil groups. Overall, the obtained data is meaningful for applications using the designed systems to deliver lipophilic ingredients.

Hormesis-Inducing Essential Oil Nanodelivery System Protects Plants against Broad Host-Range Necrotrophs.

Botrytis cinerea, a broad host-range necrotrophic (BHN) phytopathogen, establishes compatible interactions with hosts by deploying multigene infection strategies, rendering simply inherited resistance ineffective to fight off this pathogen. Since essential oils (EOs) serve as intermediators during phytobiome communication, we hypothesize that they have the potential to enhance the quantitative disease resistance against BHN by eliciting the adaptive stress response (hormesis) in plants. However, using EOs is challenging due to their poor solubility in water. Nanoemulsification of EOs enhances not only the solubility of EOs but also their potency and stability. Here, we demonstrate the potential use of essential oil nanoemulsions (EONEs) to control infections caused by BHN. Using basic engineering principles of nanocarrier design, we demonstrate the efficacy of a robust EONEs design for controlling B. cinerea infection in a model plant, Arabidopsis thaliana. Our nanoemulsion delivery system significantly enhanced the disease resistance of the host by reducing the necrotic area by up to 50% compared to untreated plants. RNA-seq analysis indicated that successful treatments upregulated autophagy, ROS scavenging, and activation of the jasmonic acid signaling pathway.

Effects of pH on ultrasonic-modified soybean lipophilic protein nanoemulsions with encapsulated vitamin E

Soybean lipophilic protein (LP) is a promising emulsifier for nanoemulsion delivery systems. Herein, the influence of pH on the stability, rheological properties, and encapsulation efficiency of a nanoemulsion formed by ultrasonically modified LP was determined, and its influence mechanism was explored. The delivery system exhibited a high absolute zeta potential value (18–30 mV) in neutral and alkaline environments (pH 7.0 or 9.0) and uniform particle size distribution (100–350 nm). Cryo-scanning electron microscopy showed that LPs in neutral and alkaline environments covered the oil–water interface more evenly than those in acidic environments. Moreover, the LP nanoemulsion has excellent rheological properties and exhibit high emulsification performance, vitamin E encapsulation efficiency, and oxidation stability. These improvements occurred because the nanoemulsion prepared using ultrasonicated LP had a high absolute zeta potential value (maximum 30 mV), small droplet size (minimum 190 nm), uniform protein film, high viscosity, and good viscoelasticity in different pH environments. In summary, the nanoemulsion delivery system prepared by LP ultrasonication can resist the influence of different pH environments and maximize the delivery efficiency in neutral and alkaline environments. The research results identified a suitable pH environment for LP nanoemulsions and provide a theoretical reference for their further application.

Interface Compositions as Determinants of Resveratrol Stability in Nanoemulsion Delivery Systems.

The incorporation of hydrophobic ingredients, such as resveratrol (a fat-soluble phytochemical), in nanoemulsions can increase the water solubility and stability of these hydrophobic ingredients. The nanodelivery of resveratrol can result in a marked improvement in the bioavailability of this health-promoting ingredient. The current study hypothesized that resveratrol can bind to caprine casein, which may result in the preservation of the biological properties of resveratrol. The fluorescence spectra provided proof of this complex formation by demonstrating that resveratrol binds to caprine casein in the vicinity of tryptophan amino acid residues. The caprine casein/resveratrol complex is stabilized by hydrophobic interactions and hydrogen bonds. Hence, to study the rate of resveratrol degradation during processing/storage, resveratrol losses were determined by reversed-phase high performance liquid chromatography (RP-HPLC) in nanoemulsions stabilized by bovine and caprine caseins individually and in combination with polysorbate-20. At 48 h oxidation, 88.33% and 89.08% was left of resveratrol in the nanoemulsions stabilized by caprine casein (αs1-I)/polysorbate-20 complex and caprine (αs1-II)/polysorbate-20 complex, while there was less resveratrol left in the nanoemulsions stabilized by bovine casein/polysorbate-20 complex, suggesting that oxygen degradation was involved. The findings of this study are crucial for the food industry since they imply the potential use of caprine casein/polysorbate-20 complex to preserve the biological properties of resveratrol.

Improving Prochlorperazine Profile by Formulating the Drug as Nanoemulsion Delivery System

Improving Prochlorperazine Profile by Formulating the Drug as Nanoemulsion Delivery System

Combination of Docetaxel with Thymoquinone in Nanoemulsion Impedes the Migration of Breast Cancer Stem Cells

Objectives: Metastatic breast cancer is an advanced stage that is highly dependent on migration signaling pathways, though it remains unclear what mechanisms control the maintenance of tumorigenic cells that drives the migration and invasion processes. This in vitro study examined the intercellular cross-talk in MCF-7 and MDA-MB-231 breast cancer cells when treated with the simultaneous administration of docetaxel (DOC) and thymoquinone (TQ) loaded in nanoemulsion (NE) delivery system. Method: The cell cycle and breast cancer stem cells (BCSC) population were evaluated using flow cytometric analysis, alongside a DNA fragmentation assessment. Further molecular investigations were performed utilizing quantitative polymerase chain reaction (Q-PCR) technique. Results: The DOC+TQ/NE formulation inhibits the proliferation of human cancer cells by the G2/M phase and S-phase cell cycle arrest in MCF-7 and MDA-MB-231 cells, receptively, and it stimulates apoptosis through induction of DNA damage. Moreover, the DOC+TQ/NE causes a significant reduction in the cellular migration activity in both cell lines as detected by the wound-healing assay. This observation could possibly be mediated through the inhibition of BCSC, accompanied by marked down-regulation of SNAIL-1 and TWIST-1 expression. Conclusion: Overall, the results demonstrate that the co-delivery of DOC and TQ within NE formulation might be considered as a promising and effective therapeutic approach for breast cancer that could prevent the intercellular signaling function of metastasis.

Intranasal delivery of topiramate nanoemulsion: Pharmacodynamic, pharmacokinetic and brain uptake studies

Epilepsy is the noncommunicable and chronic central nervous system disorder characterized by frequent, unprovoked seizures, or electrical disturbances in the brain. Topiramate is used as an antiepileptic drug for the treatment of partial onset seizures, generalized seizures and Lennox-Gastaut Syndrome. Topiramate, a BCS class II drug, has a relatively low bioavailability. It is also a substrate of P-glycoprotein and Blood Brain Barrier restricts its entry into the brain. This investigation was aimed to prepare O/W nanoemulsion delivery system of topiramate to improve its brain bioavailability. Topiramate loaded nanoemulsion was prepared by phase titration method. It was consisting of 2% w/w Capmul MCM C8, 32% w/w Tween 20:Carbitol (2:1) and 66% w/w water. It was characterized for globule size, viscosity, polydispersibility index, zeta potential, pH, conductivity values, transmittance and TEM. Pharmacodynamic, pharmacokinetic and brain drug uptake study was carried out using wistar albino rats post intranasal and oral administration. Topiramate loaded nanoemulsion was having a globule size of 4.73±0.52nm. It was stable for six months. Brain uptake of topiramate post intranasal administration of topiramate loaded nanoemulsion was significantly (P<1.86×10-8) higher when it was compared with oral administration of topiramate loaded nanoemulsion. This study indicates that intranasal administration of topiramate containing nanoemulsion could be an encouraging approach for the treatment of epilepsy to minimize the dose of topiramate in direction to avoid dose related adverse events.

Soy protein incorporated nanoemulsion for enhanced stability of probiotic (Lactobacillus delbrueckii subsp. bulgaricus) and its characterization

Abstract Nanoemulsion delivery systems are thermodynamically stable and are efficient in encapsulating the bioactive compounds, and thereby improve bioavailability of bioactive compounds. Probiotics are encapsulated in nanoemulsion to enhance their viability during storage until consumption. In the present study, an oil in water nanoemulsions were formulated with differing concentration of components by high energy method. The aqueous phase consists of soy protein isolate (SPI), gum Arabica (GA), tween 80 and oil phase consist of sunflower oil. From the result it was concluded that, emulsion stabilized by soy protein isolate in the presence of 1% tween 80 and 2% gum Arabic has good emulsifying capacity. The droplet size was

Formulation and evaluation of self nano-emulsifying drug delivery system of ezetimibe for dissolution rate enhancement

The present study was aimed to develop a Self Nano Emulsifying Delivery System of Ezetimibe (EZM) for enhancing its dissolution rate. Ezetimibe is a cholesterol absorption inhibitor, being a lipophilic drug due to its low solubility EZM shows a low dissolution profile. The SNEDDS formulation consisted of excipients Cinnamon oil, Tween 80, PEG 400 as the Oil, Surfactant and Co-surfactant. Twelve formulations with different ratios of Oil, Surfactant and Co-surfactant were prepared. The liquid SNEDDS were then converted into Solid form by adsorption technique using Avicel PH 101 and Aerosil 200 as adsorbents. The liquid SNEDDS was characterised for Particle size, Emulsification time, Dispersibility, percentage transmittance, PCM, Centrifugation, Cloud Point and Freeze thaw cycle. The solid form was characterized for the flow property, SEM, Drug content and in-vitro dissolution. Among the twelve formulations F6 formulation was found to have a particle size of 196 nm and PDI of 0.123. F6 formulation was selected as the best and it was made into solid by adsorption onto solid carriers. The F6 formulation consisted of the 25% Cinnamon oil, 50% tween 80 and 25% PEG 400. The in-vitro dissolution rate of the prepared formulation was compared with the marketed formulation. The in-vitro dissolution data showed that the drug release at the end of 60 mins from marketed formulation was 63.75 % and from SNEDDS formulation was 90.62 %. The dissolution rate of the prepared SNEDDS was increased by 1.42 times than the marketed formulation. The increase in the dissolution rate shows that SNEDDS is a suitable drug delivery system to enhance the rate of dissolution of Ezetimibe.

Role of peppermint oil in improving the oxidative stability and antioxidant capacity of borage seed oil-loaded nanoemulsions fabricated by modified starch

Borage seed oil (BSO) is one of the richest sources of γ-linolenic acid and linoleic acid, which are considered to retain plenty of health promoting benefits. However, its application in functional foods and dietary supplements remains limited owing to its superior vulnerability to oxidation. To solve this problem, ultrasound-assisted BSO-loaded nanoemulsions were prepared with modified starch incorporating different concentrations of peppermint oil (PO), as a natural antioxidant. The influence of different PO levels on the mean droplet size, rheology attributes, and oxidative stability of nanoemulsions stored at various temperatures (4, 25, and 40 °C) during 30 days storage was analyzed. In addition, DPPH and ABTS assays were used to determine the antioxidant activity and antioxidant capacity of BSO-loaded nanoemulsions, respectively. The optimized formulation (NE3; 5:5% v/v PO: BSO) exhibited a slight change in droplet size and oxidative stability at all temperatures during storage compared to other formulations. At a concentration of 328.08 μL/mL, formulation NE3 presented the minimum DPPH IC50 at 40 °C, which was lower than other formulations. The findings of this study revealed that the maximum retained antioxidant capacity (99.42 μg Trolox/mL) was related to NE3 comprising (5:5% v/v PO: BSO) stored at 40 °C for 30 days; which could be accredited to the role of PO as a natural antioxidant in order to improve the oxidative stability of nanoemulsion delivery system. Taken together, co-encapsulation of BSO and PO within nanoemulsions provides novel insights regarding the development of functional foods, dietary supplements and beverages.

Study on stability and in vitro digestion of camellia oil nanoemulsion system

The soy protein isolate (SPI) was combined with tea saponin as an emulsifier to prepare camellia oil nanoemulsion, and the stability of camellia oil nanoemulsion was compared with that of soybean protein isolate or tea saponin as emulsifier. The effects of different pH, ionic strength, heating temperature and storage time on the average particle size, ξ-potential and microstructure of camellia oil nanoemulsion prepared by three emulsifiers were studied. The results showed that the nanoemulsions prepared by combining natural emulsifiers (SPI-TS) in the pH range of 5-9 were stable and remained stable in the range of 0-300mm NaCl concentration, but had poor tolerance to high salt environment. After heating at different temperatures (30 °C-90 °C) for 30min, the average particle size, ξ-potential and microstructure of the three emulsions did not change significantly, showing good heating stability. At different storage temperatures (4, 25, 50°C) SPI-TS and TS emulsion could exist stably about four weeks, and had good storage stability. In addition, we performed in vitro simulated gastrointestinal digestion studies on the digestive properties of camellia oil nanoemulsions. The results showed that the particle size, the ξ-potential of the nanoemulsion changes depend on the type of emulsifier during digestion. The release rate of free fat acids (FFAs) of nanoemulsions after gastrointestinal digestion were all higher than that of the control group. The results showed that the nanoemulsion delivery system could effectively improve the digestion of camellia oil, It was important to improve the bioavailability of camellia oil.

Impact of calcium levels on lipid digestion and nutraceutical bioaccessibility in nanoemulsion delivery systems studied using standardized INFOGEST digestion protocol

Recently, the standardized in vitro digestion model ("INFOGEST method") used to evaluate the gastrointestinal fate of foods has been revised and updated (Brodkorb et al., 2019, Nat. Protoc., 2019, 14, 991-1014). Under fed state conditions, the calcium level used in this model is fixed and relatively low: 0.525 mM. In practice, the calcium concentration in the human gut depends on the nature of the food consumed and may vary from person-to-person. For this reason, we examined the impact of calcium concentration on the gastrointestinal fate of a model nutraceutical delivery system. The effect of calcium level (0.525-10 mM) on lipid digestion and β-carotene bioaccessibility in corn oil-in-water nanoemulsion was investigated using the INFOGEST method. At all calcium levels, the lipids were fully digested, but this could only be established by carrying out a back titration (to pH 9) at the end of the small intestine phase. Conversely, the bioaccessibility of β-carotene decreased with increasing calcium levels: from 65.5% at 0.525 mM Ca2+ to 23.7% at 10 mM Ca2+. This effect was attributed to the ability of the calcium ions to precipitate the β-carotene-loaded mixed micelles by forming insoluble calcium soaps. The ability of calcium ions to reduce carotenoid bioaccessibility may have important nutritional implications. Our results show that the bioaccessibility of hydrophobic carotenoids measured using the INFOGEST method is highly dependent on the calcium levels employed, which may have important consequences for certain calcium-rich foods. Moreover, we have shown the importance of carrying out a back titration to accurately measure free fatty acid levels in the presence of low calcium levels.

Fabrication, characterization and practical efficacy of Myristica fragrans essential oil nanoemulsion delivery system against postharvest biodeterioration.

The present study deals with encapsulation of Myristica fragrans essential oil (MFEO) into chitosan nano-matrix, their characterization and assessment of antimicrobial activity, aflatoxin inhibitory potential, safety profiling and in situ efficacy in stored rice as environment friendly effective preservative to control the postharvest losses of food commodities under storage. Surface morphology of MFEO-chitosan nanoemulsion as well as encapsulation of MFEO was confirmed through SEM, FTIR and XRD analysis. In vitro release characteristics with biphasic burst explained controlled volatilization from nanoencapsulated MFEO. Unencapsulated MFEO exhibited fungitoxicity against 15 food borne molds and inhibited aflatoxin B1 secretion by toxigenic Aspergillus flavus LHP R14 strain. In contrast, nanoencapsulated MFEO showed better fungitoxicity and inhibitory effect on aflatoxin biosynthesis at lower doses. In situ efficacy of unencapsulated and nanoencapsulated MFEO on stored rice seeds exhibited effective protection against fungal infestation, aflatoxin B1 contamination, and lipid peroxidation. Both the unencapsulated and nanoencapsulated MFEO did not affect the germination of stored rice seeds confirming non-phytotoxic nature. In addition, negligible mammalian toxicity of unencapsulated MFEO (LD50=14,289.32μL/kg body weight) and MFEO loaded chitosan nanoemulsion (LD50=9231.89μL/kg body weight) as revealed through favorable safety profile recommend the industrial significance of nanoencapsulated MFEO as an effective green alternative to environmentally hazardous synthetic pesticides for protection of food commodities during storage.

Enhanced Release Kinetics and Stability of Resveratrol Loaded Self Nanoemulsifying Delivery Systems Developed using Experimental Design

Background: Resveratrol is a member of the stilbene family emerged as a leading candidate for improving healthspan through potentially slowing the aging process and preventing chronic diseases. A number of institutions and scientists specialized in this field across the world are working to develop a promising Self Emulsifying formulation to enhance bioavailability of hydrophobic resveratrol using oil. Objective: The objective of the current study is to develop self-nano emulsifying drug delivery systems using long-chain triglycerides of resveratrol to enhance solubility, stability, release kinetics and to overcome low bioavailability. Methods: Solubility studies performed in different lipids, surfactants and cosurfactants. Phase diagrams constructed to select the areas of nanoemulsion. SNEDDS formulation was optimized using 33 central composite design considering lipid (X1), surfactant (X2) and co-surfactant (X3) as critical variables, optimized formulation was located using overlay plot. Results: The nanometer size and high values of zeta potential depicted non-coalescent nature of SNEDDS. The resulted SNEDDS formulation had improved in vitro release followed by Hixson Crowell model with higher regression R2value 0. 929. Thermodynamic stability studies ascertained stable formulation. Mean droplet size in selected nanocarrier was found to be 83.29 nm. The nanocarriers subjected to 2-8°C (45% RH), 25-30°C (60% RH) and 45-50°C (75% RH) in glass vials exhibited no significant changes in 3 months. Conclusion: The novel approach was developed by selecting optimum blends of lipids, surfactants and cosurfactant using central composite design. This study not only offers a good example of augmenting bioavailability of resveratrol but will also provide a promising oral formulation for clinical application.

Multicomponent self nano emulsifying delivery systems of resveratrol with enhanced pharmacokinetics profile

Resveratrol is a drug with high potential for clinical application based on experimental models. Though, resveratrol translation to clinical use has not been successful yet due to its poor pharmacokinetics, related to poor solubility and fast metabolism. The use of drug delivery systems, namely self-emulsifying drug delivery systems (SEDDS), may be a viable strategy to overcome the poor in vivo performance of resveratrol. In this work, a rational development of two different ternary SEDDS was conducted. Experimental data showed that quantitative variations on SEDDS composition impacted dispersion and robustness to dilution of SEDDS, as well as loading capacity and droplet size. Formulations composed of Lauroglycol® 90/Labrasol®/Capryol® PGMC (12.5/75.0/12.5) (Lau/Lab/Cap) and Tween® 80/Transcutol®/Imwitor® 742 (33.3/33.3/33.3) (T80/Trans/Imw) featured improved performance and were selected for further studies. T80/Trans/Imw formulation yield faster emulsification and originated smaller droplet size, with lower cumulative percentile of 90% of particles (D90) (below 200 nm), as compared to the than Lau/Lab/Cap formulation. Higher resveratrol permeation rate was observed in Caco-2 cell monolayer permeability studies for both formulations as compared to the free drug. Reduction of the metabolization and/or efflux of resveratrol was also noticed in the case of SEDDs, as suggested by the increased recovery of total drug. Plasmatic drug concentrations in rats observed after oral gavage indicate that both formulations provided faster resveratrol absorption than free drug, resulting in shorter Tmax values (30 min vs. 2 h). No statistically significant differences were observed for AUC0-t values of both formulations and the free drug. Still, Cmax for the Lau/Lab/Cap SEDDs formulation was 2-fold higher than for the free drug. These findings suggest that SEDDS can increase resveratrol solubility and reduce its metabolization, resulting in an overall improvement of its oral pharmacokinetics profile.

Fundamental Study on the Salt Tolerance of Oregano Essential Oil-in-Water Nanoemulsions Containing Tween 80.

This study provides fundamental information about the influence of salt on the physicochemical stability of oregano essential oil (EO) and its main components incorporated in a nanoemulsion delivery system containing Tween 80 (T80) emulsifier. The emulsion stability was found to be strongly correlated with the lipid phase composition and the type of salts. The oregano essential oil nanoemulsions remained stable for several weeks in the absence of salts. Moreover, they were insensitive to tetrabutylammonium bromide, whereas similar to carvacrol emulsions, they exhibited a rapid phase separation and oiling-off in the presence of sodium chloride. On the other hand, high oleic sunflower oil (HOSO) and p-cymene emulsions remained stable in the presence of NaCl. Addition of 70 and 80% HOSO to the lipid phase of oregano EO and carvacrol, respectively, was found to be sufficient for the formation of emulsions with a high stability to 1.7 M NaCl. Hereby, the morphology of the oregano EO emulsions after 30 days of storage in the presence of NaCl was visualized using a transmission electron microscope. The determination of the surface load and area per surfactant molecule by interfacial tension (IFT) measurements and quartz crystal microbalance with dissipation revealed the dehydration of the polyoxyethylene groups of T80 in the presence of salt. The thickness of the T80 adsorbed layer onto solid hydrophobic and hydrophilic surfaces was significantly lower (p < 0.05) in the presence of sodium chloride. It is hypothesized that a combination of Ostwald ripening and coalescence due to an IFT increase and dehydration was responsible for the instability of the emulsions containing the more polar oregano EO and carvacrol in the presence of salt. The results obtained in this study could be useful for the formulation of essential oil nanoemulsions in the presence of salts applicable in food, pharmaceutical, and personal care products.

Challenging the CNS Targeting Potential of Systemically Administered Nanoemulsion Delivery Systems: a Case Study with Rapamycin-Containing Fish Oil Nanoemulsions in Mice.

Despite extensive preclinical investigations, in-vivo properties and formulation characteristics that improve CNS drug delivery following systemic dosing of nanoemulsions remain incompletely understood. The CNS targeting potential of systemically administered nanoemulsions was evaluated by formulating rapamycin containing fish oil nanoemulsions, and testing the combined effect of formulation characteristics such as the circulation half-life and particle size distribution, on CNS delivery of rapamycin containing fish oil nanoemulsions in mice. Results generated with rapamycin nanoemulsions suggested that circulation half-life and particle size distribution did not impact the brain targeting efficiency of rapamycin containing fish oil nanoemulsions. Further, in the absence of any improvement in the systemic exposures of rapamycin, nanoemulsions did not outperform their aqueous counterpart with respect to the extent of CNS drug delivery. Our findings confirm that BBB penetration, which primarily depends on intrinsic drug-related properties, may not be significantly improved following encapsulation of drugs in nanoemulsions. Graphical Abstract The CNS targeting potential of systemically administered nanoemulsions was investigated by formulating various rapamycin containing fish oil nanoemulsions associated with different formulation characteristics such as the circulation half-life and particle size distribution. The targeting efficiency (TE) defined as the ratio of the brain exposures to the accompanying systemic exposures of rapamycin was estimated for each formulation following IV dosing in mice.

Preparation and evaluation of protective effect of pumpkin seed oil based self nanoemulsifying oral delivery system against ibuprofen-induced peptic ulcer

BackgroundIbuprofen (IB) is a potent non-steroidal anti-inflammatory drug but of limited use due to low solubility and gastric ulceration side effect. ObjectiveTo utilize pumpkin seed oil in the form of self nanoemulsion delivery system (SNEDs) as an enhancer for ibuprofen solubility, and a protective factor against ibuprofen-induced peptic ulcer. MethodPseudo-ternary phase diagrams were utilized to determine the self-emulsifying region. The effects of formulation variables, i.e., concentrations of pumpkin oil (X1), polyethylene glycol-40 stearate (MYS-40MV) as a surfactant (X2), and polyethylene glycol-60 hydrogenated castor oil (HCO-60) as cosurfactant, on globule size and anti-ulcerative activity were evaluated. ResultsOptimum levels of IB-SNEDs components indicated by mixture design were X1(26.5%), X2(63.5%), and X3(10%), respectively. The optimized formula showed globule size of 104 nm. The anti-ulcerative activity score of the optimized formulation was 0.5, indicating a potential anti-ulcerative effect result from incorporation of pumpkin oil as one of IB-SNEDS component, in comparison to score 4 and 5 for the marketed product, and formulation containing oleic acid as an oil, respectively. ConclusionPumpkin seed oil-based SNEDS enhanced the solubility and protected against ulceration effect of ibuprofen. The study suggests that pumpkin seed oil can effectively address the limitation of ibuprofen-induced gastric ulcer.