Submicron Emulsions Research Articles

Comparison of the in vitro cytotoxicity among phospholipid-based parenteral drug delivery systems: Emulsions, liposomes and aqueous lecithin dispersions (WLDs)

Lecithin and isolated phospholipids (mainly phosphatidylcholine) have been used for years as pharmaceutical excipients in parenteral formulations: submicron emulsions, liposomes and mixed micelles. Under development are also other lecithin-based drug delivery systems, e.g. aqueous lecithin dispersions (WLDs). The aim of the study was to investigate the properties and potential cytotoxicity of 7 different phospholipid-based dispersions intended for parenteral administration: emulsions, liposomes and WLDs. Each formulation contained egg phosphatidylcholine (PC) in the concentration range of 0.6–5.0%, and to some formulations other surfactants, such as polysorbate 80 (P80), Solutol HS 15 (HS) and cholesterol (Ch) were added. Particles in all dispersions were homogenous (PDI < 0.26) and submicron in size (Z-average in the range of approx. 100–260 nm). The cytotoxicity of all tested formulations was evaluated by means of 3 independent methods: a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, a real-time xCELLigence (RTCA) system, and a flow cytometry analysis, using two cell lines: human embryonic kidney 293 (HEK-293) and human promyelocytic leukaemia (HL-60). The results indicated that regardless of the test method and cell line type, the cytotoxicity of all formulations was low, especially when dispersions diluted to concentrations of =10% were tested. A more pronounced cytotoxic effect was noticed only for the following formulations: E-P80 (emulsion containing P80), WLD (unbuffered aqueous lecithin dispersion) and L-Ch (liposomes containing Ch), tested as less diluted (concentration 10% or 25%). IC50 values measured for these dispersions (on HL-60 cells) amounted to: 10.4 ± 0.5% (v/v), 14.4 ± 0.2% (v/v) and 24.2 ± 0.6% (v/v), respectively. Our investigation confirmed the biocompatibility of all tested phospholipid-based formulations: emulsions, liposomes and also newly-developed WLDs, which can be considered as safe parenteral drug carriers.

Spontaneous Formation of Flavor Oil Emulsions by Using Sucrose Esters and Emulsion Stability Study

This work aimed to prepare natural flavor oil emulsions by spontaneous emulsification by adding organic mixtures consisting of flavor oils, sucrose esters, and with/without ethanol into a stirred aqueous phase. Orange oil (OrO), peppermint oil (PpO), sucrose esters with mainly sucrose monostearate (S1670), and sucrose esters with mainly sucrose monopalmitate (P1670) were employed. The mean droplet sizes of emulsions were strongly dependent on flavor oil types, flavor oil concentrations, sucrose ester concentrations, and stirring speeds, but were lesser dependent on sucrose ester types. Higher sucrose ester concentrations and stronger convection created smaller oil droplets. The smallest mean droplet size of ~200 nm was achieved by the formulation of OrO emulsions containing 10.0 wt% oil, 7.5 wt% sucrose esters, and < 1 wt% ethanol. OrO emulsions stabilized by sucrose esters exhibited good physical stability over one month storage while PpO emulsions destabilized rapidly, suggested by Ostwald ripening. This study revealed that sucrose esters can be applied to form submicron emulsions without using any high energy homogenizers.

Development of rosemary essential oil nanoemulsions using a wheat biomass-derived surfactant.

In the present work aqueous-based emulsions formulated with bio-based solvents and surfactants were studied. The droplet size distribution, rheology and physical stability of rosemary essential oil/water emulsions formulated with an emulsifier derived from wheat waste (alkyl polypentoside) were investigated as a function of the dispersed phase concentration (10-50 wt%) by means of laser diffraction, multiple light scattering and rheology measurements. Subsequently, processing variables, such as the pressure and the number of microfluidization passes, were studied to the best formulation (20 wt% rosemary oil). The laser diffraction technique revealed that monodispersed submicron emulsions were obtained for oil phase concentrations below 20 wt%. All emulsions showed Newtonian behavior, except for the emulsion containing 50 wt% oil, which exhibited shear-thinning properties. Moreover, the main destabilization mechanism of all the emulsions was creaming. The combination of techniques used demonstrated that the emulsion containing 20 wt% rosemary essential oil (REO) and prepared by microfluidization at 2500 psi (17.2 MPa) exhibited the longest physical stability and the smallest droplet size after 3passes. This research is a contribution to sustainable development not only by using chemicals derived from renewable raw materials but also by achieving stable emulsions with a low surfactant/oil mass ratio.

Ethyl oleate food-grade O/W emulsions loaded with apigenin: Insights to their formulation characteristics and physico-chemical stability

Apigenin has attracted a great interest in the food industry due to the wide range of its biological activities including antioxidant and anti-inflammatory. The encapsulation of apigenin in oil-in-water (O/W) emulsions could overcome its low solubility and lead to the development of new functional food products. The aim of this study is to formulate food-grade O/W submicron emulsions loaded with apigenin using high-pressure homogenization. Supersaturated solutions of 0.1 wt% apigenin in ethyl oleate were heated at 100 °C for 30, 60, or 120 min and the supernant after centrifugation were used as to-be-dispersed phases. An aqueous solution containing 1 wt% tween 20 was used as the continuous phase. We examined the effect of heating process of the ethyl oleate prior to emulsification and the homogenization-pressure (60–150 MPa) on the physico-chemical characteristics of the O/W emulsions immediately after formulation and during storage. Submicron O/W emulsions were formulated and the lowest average droplet diameter (dav) was 169 ± 2.082 nm with a polydispersity index (PDI) of 0.06 ± 0.002. After 30 days of storage at 4 °C, the O/W emulsion formulated remained physically stable with little change in their dav and PDI values. The preheat treatment of ethyl oleate, affected the initial loaded apigenin concentration but hardly affected the physico-chemical stability of O/W emulsions. However, HPLC analysis demonstrated that the emulsification pressure was a relevant parameter affecting apigenin retention during the storage of O/W emulsions. Apigenin degradation in ethyl oleate O/W emulsions followed zero order kinetics and about 91.5–93.5% of apigenin could be retained in O/W emulsions after 30 days of storage.

DNA-Coated Functional Oil Droplets.

Many industrial soft materials include oil-in-water (O/W) emulsions at the core of their formulations. By using tuneable interface stabilizing agents, such emulsions can self-assemble into complex structures. DNA has been used for decades as a thermoresponsive, highly specific binding agent between hard and, recently, soft colloids. Up until now, emulsion droplets functionalized with DNA had relatively low coating densities and were expensive to scale up. Here, a general O/W DNA-coating method using functional nonionic amphiphilic block copolymers, both diblock and triblock, is presented. The hydrophilic poly(ethylene glycol) ends of the surfactants are functionalized with azides, allowing for efficient, dense, and controlled coupling of dibenzocyclooctane-functionalized DNA to the polymers through a strain-promoted alkyne-azide click reaction. The protocol is readily scalable due to the triblock's commercial availability. Different production methods (ultrasonication, microfluidics, and membrane emulsification) are used with different oils (hexadecane and silicone oil) to produce functional droplets in various size ranges (submicron, ∼20 and >50 μm), showcasing the generality of the protocol. Thermoreversible submicron emulsion gels, hierarchical "raspberry" droplets, and controlled droplet release from a flat DNA-coated surface are demonstrated. The emulsion stability and polydispersity is evaluated using dynamic light scattering and optical microscopy. The generality and simplicity of the method opens up new applications in soft matter, biotechnological research, and industrial advances.

FORMULATION AND EVALUATION OF SUBMICRON EMULSION CONTAINING ENTRAPPED FLUOROQUINOLONE FOR OCULAR DELIVERY

Objective: The objective of the present work was to develop and characterize the submicron emulsion bearing antimicrobial drug sparfloxacin for improvement of ocular activity by improved retention in eyes. The developed delivery system was results with prolonged drug release as compared to the conventional dosage form.Methods: SE prepared by high energy emulsification and sonication to obtain uniform globule size.Results: Average internal droplets size of the optimized formulation was 0.278±0.6 μm, pH of the optimized formulation was 6.9±0.6 (average of three determinations), and viscosity 2.9±0.5 cps suitable for ocular use. Entrapment of SF was 63±3.4%. Stable under accelerated and long-term at 4°C and 37°C. No major changes reported on pH and viscosity of optimized formulations. In vitro, drug release pattern showed sustain release of SF, a cumulative percent release of SF was found 87.8±1.7% within 24 h. Transmission electron microscopy showed spherical shape and size within 1 μm.Conclusion: Designed formulation can be a good candidate for ocular drug delivery for severe ocular infections where frequent dosing required for conditions such as endophthalmitis, corneal ulcer, and penetrating trauma.

Submicron emulsion of cinnamaldehyde ameliorates bleomycin-induced idiopathic pulmonary fibrosis via inhibition of inflammation, oxidative stress and epithelial-mesenchymal transition

AimsIdiopathic pulmonary fibrosis (IPF) is the most frequent and severe form of idiopathic interstitial pneumonias. The pathogenesis is associated with inflammation and oxidative stress and epithelial-mesenchymal transition (EMT). Cinnamaldehyde exhibits antiinflammatory and antioxidant properties, but its effect on IPF is unknown. The present study is to investigate the anti-fibrotic effect and action mechanism of cinnamaldehyde on IPF. Materials and methodsIPF was induced by intratracheal bleomycin in mice. Submicron emulsion of cinnamaldehyde was given by intraperitoneal injection once everyday for 7 or 21 continuous days after bleomycin administration. Lung histological and injury indexes were analyzed. The protein expressions of inflammation and oxidative stress as well as EMT markers alpha-smooth muscle actin (α-SMA) and E-cadherin in mice and cultured A549 cells were measured. ResultsCinnamaldehyde attenuated the bleomycin-induced histological injury, reduced hydroxyproline level and improved pulmonary function by the inhibiting inflammatory cytokines and reactive oxygen species production as well as enhancing total superoxide dismutase activity in bleomycin-induced mice. Cinnamaldehyde also inhibited EMT in both bleomycin-induced mice and TGF-β1-stimulated A549 cells. ConclusionsCinnamaldehyde ameliorated bleomycin-induced IPF via inhibition of inflammation and oxidative stress and EMT.

Urinary metabolomics study of Xiangdan submicron emulsions on a rat model of myocardial ischaemia

ObjectiveThe aim of this study was to discover the potential biomarkers changes on a rat model of isoproterenol (ISO) induced myocardial ischaemia before and after treatment with a Xiangdan submicron emulsion and to explore the unclearing mechanisms by urinary metabolomics. MethodsThree active traditional Chinese medicine (TCM) ingredients were formulated into a lyophilized submicron emulsion powder with hydroxypropyl-β-cyclodextrin encapsulation by high pressure homogenization technology. The three ingredients were given both separately and combined, and the corresponding effects of the three drugs were compared. Principal component analysis (PCA) and the HPLC-UV analytical method was applied to explore the change of composition of urine metabolites in a rat model of isoproterenol induced myocardial ischaemia. ResultsAnalytical methods measuring the three active ingredients in urine samples were established. PCA score plots revealed that the therapeutic effect of the Xiangdan submicron emulsion was more significant than that of the Xiangdan injection. There was a synergistic effect among the three active ingredients. Furthermore, studies of rat metabolism changes and structure analysis of biological markers indicated that the mechanism of Xiangdan formulations was related to the inhibition of abnormal tryptophan metabolism. ConclusionXiangdan preparations had a confirmed effect in the treatment of coronary heart disease, especially with the novel Xiangdan submicron emulsion formulation. Urinary metabolomics methods to monitor special biomarker changes is an excellent method to reveal the mechanism of action of TCM drugs.

Influence of essential oils and pectin on nanoemulsion formulation: A ternary phase experimental approach

A pseudo-ternary phase experimental approach was used to model the influence of the mixture components concentration on the nanoemulsions properties as ternary systems. For this, several types of essential oils (EO) were used as lipid phase, being oregano (OR-EO), thyme (TH-EO), lemongrass (LG-EO) and mandarin (MN-EO), while pectin and Tween 80 were studied as emulsifiers. All formulations were processed by microfluidization at 150 MPa and 5 cycles. Polynomial models were fitted to experimental data and their adjusted R2 and p-values were obtained. Remarkably, a pectin concentration of 1% (w/w) allowed the formation of submicron emulsions between 350 and 850 nm in the absence of Tween 80 for all the studied EOs, thus confirming its emulsification capacity. In general, increasing the pectin concentration up to 2% (w/w) enlarged the particle size of emulsions and their viscosity thus suggesting decreased emulsification efficiency during microfluidization. Nonetheless, nanoemulsions with particle sizes below 500 nm were obtained when a minimum Tween 80 concentration of 1.8% (w/w) was used, regardless the pectin or EO concentrations. The modest decrease in the ζ-potential that was observed depending on the type of EO at increasing pectin concentrations indicated that pectin is not or weakly adsorbed at the oil-water interface. All nanoemulsions were transparent at high surfactant and low EO concentrations due to a weak light scattering of the nano-sized oil droplets. Thus, this work contributes in elucidating the role of pectin and small molecule non-ionic surfactants on the formation of submicron emulsions and nanoemulsions containing essential oils.

Combination of Phospholipid Complex and Submicron Emulsion Techniques for Improving Oral Bioavailability and Therapeutic Efficacy of Water-Insoluble Drug.

Water-insoluble drugs cannot be absorbed effectively through the gastrointestinal tract due to insufficient solubility and often face the problems of low bioavailability and poor therapeutic efficacy. To overcome these biopharmaceutical challenges, lipid-based formulations were suggested and have been researched in recent years. In this study, we used atorvastatin as a model drug to prepare a phospholipid complex prodrug system to upgrade its lipophilicity and further developed a drug loaded submicron emulsion to improve its in vivo bioavailability. The mean particle size and zeta potential of submicron emulsion were 122.7 nm and -22.7 mV. Intestinal absorption of atorvastatin from submicron emulsion was significantly improved compared with free drug, and the absorption rate constant ( Ka) and apparent permeability coefficients ( Papp) increase 2.88-fold and 2.45-fold, respectively. After oral administration, the atorvastatin plasma concentration of the emulsion group was much higher than that of free drug and the area under the curve (AUC) reached to 4.033 mg/L·h (2.58-fold). In vivo pharmacodynamics results revealed that atorvastatin submicron emulsion showed excellent antihyperlipidemia efficacy by reducing the total cholesterol, triglyceride, and low density lipoprotein cholesterol (LDL-cholesterol) levels and simultaneously increasing the high density lipoprotein cholesterol (HDL-cholesterol) level in comparison with Lipitor. In conclusion, drug-phospholipid complex loaded submicron emulsion was a promising oral delivery system for improving in vivo absorption behavior and therapeutic efficacy for water-insoluble drugs.

Antioxidant Activity, In Vitro Digestibility and Stability of Flaxseed Oil and Quercetin Co‐Loaded Submicron Emulsions

Flaxseed oil and quercetin have received extensive attention in food industry. However, their poor solubility in water and stability are major limitations for their application in functional foods. In this work, we encapsulated flaxseed oil and quercetin into submicron emulsions by high pressure homogenization method to overcome their shortcomings in application. The loading of flaxseed oil in submicron emulsions was 10% and the solubility of quercetin in water is increased by at least 1300 folds. In vitro antioxidant study indicated that the addition of flaxseed oil could increase the antioxidant activity of quercetin. During in vitro digestion, the smaller the particle size of submicron emulsions, the faster the digestive rate of flaxseed oil and the higher the bio‐accessibility of quercetin. Furthermore, accelerated oxidation study revealed that quercetin could protect flaxseed oil effectively. Besides, metallic ions stability study illustrated that the influence of Na+ on the emulsion stability is smaller than that of Ca2+ and high Ca2+ concentration could lead to stratification of the submicron emulsions. The storage stability shows that the prepared submicron emulsions can be stored for 8 weeks at three different temperatures. Hence, submicron emulsion can be a promising vehicle for delivery of flaxseed oil and quercetin.Practical Applications: Submicron emulsions can be used to improve the water solubility and bioavailability of lipophilic nutrients. The combination of flaxseed oil and quercetin in submicron emulsions can compensate for their individual shortcomings in application and exert synergistic beneficial actions on human health. Furthermore, this technology is easy in operation and can be realized in industry. Flaxseed oil and quercetin co‐loaded submicron emulsions can be applied in milk and liquid beverages in food industry.Submicron emulsions are fabricated to enhance the delivery of flaxseed oil and quercetin. The smaller the particle size of submicron emulsions, the faster the digestive rate of flaxseed oil and the higher the bio‐accessibility of quercetin. Quercetin can protect flaxseed oil against oxidation effectively. The antioxidant effect of quercetin is found to be better than commonly used antioxidants.

Self-Emulsifying Granules and Pellets: Composition and Formation Mechanisms for Instant or Controlled Release.

Many articles have been published in the last two decades demonstrating improvement in the dissolution and absorption of low solubility drugs when formulated into self-emulsifying drug delivery systems (SEDDS). Several such pharmaceutical products have appeared in the market for medium dose (Neoral® for Cyclsoprin A, Kaletra® for Lopinavir and Ritonavir), or low dose medications (Rocaltrol® for Calcitriol and Avodart® for Dutasteride). However, these are in the form of viscous liquids or semisolid presentations, characterized by the disadvantages of high production cost, stability problems and the requirement of large quantities of surfactants. Solid SEDDS (S-SEDDS), as coarse powders, granules or pellets, besides solubility improvement, can be filled easily into capsules or processed into tablets providing a handy dosage form with instant release, which can be further developed into controlled release by mixing with suitable polymers or coating with polymeric films. In this review, the materials used for the preparation of S-SEDDS, their properties and role in the formulations are detailed. Factors affecting the physical characteristics, mechanical properties of S-SEDDS as well as their in vitro release and in vivo absorption are discussed. The mechanisms involved in the formation of instant and sustained release self-emulsifying granules or pellets are elucidated. Relationships are demonstrated between the characteristics of S-SEDDS units (size, shape, mechanical properties, re-emulsification ability, drug migration and drug release) and the properties of the submicron emulsions used as massing liquids, with the aim to further elucidate the formation mechanisms. The influence of the composition of the powdered ingredients forming the granule or pellet on the properties of S-SEDDS is also examined. Examples of formulations of S-SEDDS that have been reported in the literature in the last thirteen years (2004–2017) are presented.

Ultrasound-mediated nettle oil nanoemulsions stabilized by purified jujube polysaccharide: Process optimization, microbial evaluation and physicochemical storage stability

Optimizing the manufacturing conditions of stable oil-in-water submicron emulsions using ultrasound assisted emulsification is a critical challenge in food and bio-industries. The influence of irradiation time (IT, 5–25min) and ultrasonic applied power (UAP, 50–250W) was studied on formation of stinging nettle essential oil (1.25wt%)-nanoemulsions (SNEO-NEs) in aqueous solution of purified jujube polysaccharide (JCP-1, 1.5wt%). Use of the single-factor and response surface methodologies showed an UAP of 165.87W and an IT of 23.64min can result in the best NE physicochemical properties including 86.75 nm droplet size, 0.079 polydispersity index, 1.331 refractive index, 34.5mN/m surface tension, 4.49mPa·s viscosity, 0.958meqO2/kg oil peroxide value and 0.814 anisidine value. Kinetic analysis of stability and antioxidant losses of the optimal SNEO-NEs stored for 45 days demonstrated although there was no substantial difference in the droplets growth between 4 and 25°C, a lower oxidative stability rate (24.1%) was monitored at 4°C. The Gram-positive bacterium also was more inactivated by the optimal NE compared with the Gram-negative one (P<0.05). This novel NE-based delivery system can be a successful strategy for the controlled release of other poorly water-soluble components with the improved functionalities.

Lipid digestion, micelle formation and carotenoid bioaccessibility kinetics: Influence of emulsion droplet size.

Carotenoid-enriched oil-in-water emulsions with different droplet sizes (small: d43 0.72μm; medium: d43 1.9μm; large: d43 15.1μm) were subjected to simulated gastrointestinal conditions. The kinetics of lipolysis, micelle formation and carotenoid bioaccessibility were monitored during the intestinal phase. The rates of all three processes increased with decreasing droplet size. The large droplet size emulsion contained undigested oil at the end of digestion, whereas an almost complete hydrolysis was observed for the other two emulsions. The sub-micron emulsion presented a higher conversion of MAGs to FFAs during digestion, which led to a higher concentration of FFAs in the mixed micelles. The incorporation of carotenoids into mixed micelles occurred faster and reached a higher final value for the small droplet size emulsion, leading to final carotenoids bioaccessibility values of around 70%. This work provides valuable information for developing in silico models to simulate the lipid digestibility and carotenoid bioaccessibility.

P.1.001 - Receptor activator of NF-κB is involved in vitamin D3 deficiency-mediated neurotoxicity in rats induced by prednisolone

The aim of this study was to discover the potential biomarkers changes on a rat model of isoproterenol (ISO) induced myocardial ischaemia before and after treatment with a Xiangdan submicron emulsion and to explore the unclearing mechanisms by urinary metabolomics.Three active traditional Chinese medicine (TCM) ingredients were formulated into a lyophilized submicron emulsion powder with hydroxypropyl-β-cyclodextrin encapsulation by high pressure homogenization technology. The three ingredients were given both separately and combined, and the corresponding effects of the three drugs were compared. Principal component analysis (PCA) and the HPLC-UV analytical method was applied to explore the change of composition of urine metabolites in a rat model of isoproterenol induced myocardial ischaemia.Analytical methods measuring the three active ingredients in urine samples were established. PCA score plots revealed that the therapeutic effect of the Xiangdan submicron emulsion was more significant than that of the Xiangdan injection. There was a synergistic effect among the three active ingredients. Furthermore, studies of rat metabolism changes and structure analysis of biological markers indicated that the mechanism of Xiangdan formulations was related to the inhibition of abnormal tryptophan metabolism.Xiangdan preparations had a confirmed effect in the treatment of coronary heart disease, especially with the novel Xiangdan submicron emulsion formulation. Urinary metabolomics methods to monitor special biomarker changes is an excellent method to reveal the mechanism of action of TCM drugs.

Development of edible films obtained from submicron emulsions based on whey protein concentrate, oil/beeswax and brea gum.

Edible films with whey protein concentrate (WPC) with a lipid component, sunflower oil (O) or beeswax (W), to enhance barrier to water vapor were obtained. Brea gum was used as emulsifier and also as matrix component. In order to achieve emulsion with small and homogeneous droplet size, an ultrasonicator equipment was used after obtaining a pre-emulsion using a blender. The films were made by casting. Effects of lipid fraction on droplet size, zeta potential, mechanical properties, water vapor permeability (WVP), solubility, and optical properties were determined. The droplet size of emulsions with BG decreased when decreasing the lipid content in the formulation. The zeta potential was negative for all the formulations, since the pH was close to 6 for all of them and pI of BG is close to 2.5, and pI of ß-lactoglobulin and α-lactalbumin (main proteins in WPC) are 5.2 and 4.1, respectively. Increasing W or SO content in blended films reduced the tensile strength and puncture resistance significantly. BG and WPC films without lipid presented better mechanical properties. The presence of lipids decreased the WVP, as expected, and those films having BG improved this property. BG films were slightly amber as a result of the natural color of the gum. BG has shown to be a good polysaccharide for emulsifying the lipid fraction and improving the homogeneity and mechanical properties of the films with WPC and beeswax or oil.

Submicron O/W emulsions embedded into modified waxy maize starch based matrix: Rheological and microstructural characterization

The aim of this study was to investigate the rheological properties and storage stability of submicron O/W emulsions formulated with dried skim milk and vegetable oil at neutral pH, and to analyse the impact of their inclusion into starch suspension. Sunflower oil droplets were pre-emulsified in skim milk suspension by a rotor-stator homogenizer and further an ultrasonic treatment was applied. Droplets sizes decreased after applying ultrasound (US) from 1.4 to 0.4 μm (d32). Emulsions exhibited Bingham flow behaviour and the plastic viscosity increased upon 14 days of storage at 5 °C. Flocculation may be responsible for the increase in viscosity with aging time. Mixed colloidal dispersions (submicron emulsions embedded into starch matrix) showed shear-thinning behaviour. Over storage, light microscope micrographs suggested deposited droplets on the starch granules surface. Flow and viscoelastic behaviour of mixed colloidal dispersions indicated droplets flocculation, attributable to a reversible depletion mechanism of destabilization.

Low density lipoprotein peptide conjugated submicron emulsions for combating prostate cancer.

Submicron emulsions (SEs) is an advanced formulation that possesses good biocompatibility, high loading of hydrophobic drugs, and good stability through autoclave sterilization. To enhance tumor targeting and tumor cell uptake, SEs could be modified with positive charge and targeting moieties. In the present study, three formulations were prepared: Docetaxel-loaded SEs (DocSEs), cationic DocSEs (DocCSEs), and low density lipoprotein receptor (LDLR) targeted peptide-RLT (CEKLKEAFRLTRKRGLKLA) modified DocCSEs (RLT-DocCSEs). The optimized RLT-DocCSEs showed a particle size 182.2±10nm, a zeta potential 39.62±2.41mV, and a loading efficiency of Docetaxel (Doc) 98%. RLT-DocCSEs demonstrated sustained release in 96h and was stable for two months at 4°C. Compared to DocSEs and DocCSEs, RLT-DocCSEs caused significantly more PC-3 cell inhibition and cell apoptosis. RLT-DocCSEs also showed more cellular uptake and slower cellular elimination than that of DocSEs and DocCSEs. The present study indicated RLT-DocCSEs could be a potential formulation for injection of anti-cancer therapeutics with increased tumor targeting and anti-tumor efficacy.

Optimization of nanoemulsions processed by high-pressure homogenization to protect a bioactive extract of jackfruit (Artocarpus heterophyllus Lam)

The present work investigates the development of an eco-friendly nanoemulsion to maintain the bioactivity of a rich in carotenoids extract from jackfruit (Artocarpus heterophyllus Lam) pulp. Firstly, the influence of the sucrose monostearate (SMS) content (0.5–2%, w/w), miglyol content (5–20%, w/w) and homogenization pressure (400–800 bar) on the droplet size distribution, rheology and stability of emulsions processed by high-pressure homogenization was studied. Except two formulations containing the highest SMS content and processed at the lowest pressure, stable fluid submicron emulsions were obtained. Then, a jackfruit pulp extract was incorporated in the oily phase of the selected emulsion (5% miglyol plus 0.5% SMS processed twice in a high-pressure homogenizer at 800 bar). The antioxidant activity of the jackfruit extract loaded in the selected emulsion stored at 4 °C has exhibited a longer stability compared to the same extract only dissolved in miglyol and stored in same conditions.

Physical stability of N,N-dimethyldecanamide/α-pinene-in-water emulsions as influenced by surfactant concentration

In recent years, interest in submicron emulsions has increased due to their high stability and potential applications in the encapsulation and release of active ingredients in many industrial fields, such as the food industry, pharmaceuticals or agrochemicals. Furthermore, the social demand for eco-friendly solutions to replace hazardous solvents in many dispersion formulations has steadily risen. In this study, the influence of surfactant concentration on the formation and physical stability of submicron oil-in-water emulsions using a high-pressure dual-channel homogenizer (microfluidizer) has been investigated. The formulation involved the use of a blend of two green solvents (N,N-dimethyldecanamide and α-pinene) as dispersed phase and a nonionic polyoxyethylene glycerol ester derived from coconut oil as emulsifier (Levenol® C-201), which enjoys a European eco-label. Therefore, these emulsions may find applications as matrices for agrochemicals. Physical stability and rheological properties of the emulsions studied showed an important dependence on the eco-friendly surfactant concentration. The lowest surfactant concentration (1wt%) yielded the onset of a creaming process after a short aging time and was not enough to avoid recoalescence during emulsification. On the other hand, the higher surfactant concentrations (4–5wt%) resulted in depletion flocculation, which in turn triggered emulsion destabilization by coalescence. The optimum physical stability was exhibited by emulsions containing intermediate surfactant concentrations (2–3wt%) since coalescence was hardly significant and the onset of a weak creaming destabilization process was substantially delayed.