Spontaneous Emulsification Research Articles

Preparation and in vitro evaluation of rhein-loaded PEG-PCL-PEI nanoparticles

This study was aimed to synthesize the polyethyleneglycol-polycaprolactone-polyethyleneimine (PEG-PCL-PEI) three block polymer material, prepareRhein (RH)-loaded PEG-PCL-PEI nanoparticles(PPP-RH-NPS), and then evaluate their physical and chemical properties and biological characteristics in vitro. PEG-PCL-PEI polymer was obtained by adopting thering-opening polymerization and Michael addition reaction, and their physical and chemical properties were analyzed by using NMR and gel permeation chromatography. PEG-PCL-PEI was then used as the carriers to prepare PPP-RH-NPS by applying spontaneous emulsification solvent diffusion method. The results showed that molecular weight of PEG-PCL-PEI polymer was 9.5×103, and critical micelle concentration was 0.723 mmol•L⁻¹. PPP-RH-NPS had pale yellow, opalescence faade, round and smooth without aggregation, formed of (118.3±3.6) nm in particle size with PDI of (0.19±0.08), Zeta potential of (6.3±1.5) mV, entrapment efficiency of (93.64±5.28)%, and drug loading of (8.57±0.53)%. The accumulative release percentage of PPP-RH-NPS was 75.92% in 48h, and the release profiles in PBS conformed to the Higuchi equation： Q=0.121 6t1/2+0.069 5 (R²=0.887 4), presenting slow release characteristics. Within the scope of the 0-0.05 mmol•L⁻¹, the nanoparticles had no obvious hemolysis on rabbit red blood cells and toxicity on HK-2 cells. In the investigation of uptake efficiency by flow cytometry, nanoparticles can be absorbed into cells quickly and internalized within 30 minutes fully, with a high uptake efficiency. In confocal laser scanning microscope observation, the nanoparticles can escape from lysosome into cytoplasm. Herein, this study synthesized the PEG-PCL-PEI polymer and prepared PPP-RH-NPS successfully; the nanoparticles showed uniform particle size, higher encapsulation efficiency and drug-loading rate, slow release characteristics, quick uptake and internalization, lysosome escape property and good biocompatibility. PPP-RH-NPS will be a promising pharmaceutical formulation for further development.

Magnetic Nanoemulsions: Comparison between Nanoemulsions Formed by Ultrasonication and by Spontaneous Emulsification.

Nanoemulsions are particularly suitable as a platform in the development of delivery systems. The type of nanoemulsion with a higher stability will offer an advantage in the preparation of a delivery system for lipophilic drugs. Nanoemulsions can be fabricated by different processing methods, which are usually categorized as either high- or low-energy methods. In this study, a comparison between two methods of preparing magnetic oil-in-water (O/W) nanoemulsions is described. The nanoemulsions were formed by sonication (the high-energy method) or by spontaneous emulsification (the low-energy method). In both cases, the oil phase was olive oil, and a phospholipid and a pegylated phospholipid were used as emulsifiers. To favor the comparison, the amounts of the components were the same in both kinds of nanoemulsions. Moreover, nanoemulsions were loaded with hydrophobic superparamagnetic nanoparticles and indomethacin. In vitro, releases studies indicated a short drug burst period followed by a prolonged phase of dissolutive drug release. The Korsmeyer-Peppas model can fit the associated kinetics. The results showed that such nanoemulsions are suitable as a platform in the development of delivering systems for lipophilic drugs. The long-term stability was also examined at different temperatures, as well as the interaction with plasma proteins. Nanoemulsion obtained by the low-energy method showed a great stability at 4 °C and at ambient temperature. Its size and polydispersity did not change over more than two months. The spontaneous emulsification method therefore has great potential for forming nanoemulsion-based delivery systems.

Nanoemulsion - An ideal drug delivery for nose-to-brain targeting

Nanoemulsions are well-liked drug delivery system in the pharmaceutical world. These are clear, thermodynamically stable and isotropic liquid-in-liquid dispersion with an average size range of 20 to 200 nm. They are having elevated surface area, strong stability, optically clear appearance, acceptable rheology and good drug loading capacity because of their characteristic droplet size. The methods used for the preparation of nanoemulsions include bubble bursting method, micro-fluidization, phase inversion temperature, emulsion inversion point, ultrasonication and spontaneous emulsification high-pressure homogenization etc. In the present paper, the advantages, methods of preparation and applications of nanoemulsions are critically reviewed.

Spontaneous Emulsification as a Function of Material Exchange

Direct visualization at 1873 K of 0% to 8% molten FeAl droplets suspended in a SiO2 enriched oxide medium was carried out to image the evolution of droplet morphology during reaction between Al and SiO2. Phenomena such as perturbation growth, necking and budding of offspring droplets from a bulk body are observed. The observations are used to discuss and inform a new approach to the nature of interfacial tension and the impact this has on concepts used to define interfacial tension for a two phase system with material exchange across the interface. The mapping of global interfacial tension coupled with free energy dissipation has been used to give an energetic reasoning as to the behaviour seen with respect to aluminium content in the metal phase.

Fabrication of chia (Salvia hispanica L.) seed oil nanoemulsions using different emulsifiers

In this study, the quality of spiral cold press chia seed oil was evaluated and four types of O/W chia seed oil nanoemlusion systems were prepared, including chia seed oil nanoemulsion stabilized with Tween 80 and Span 80 by spontaneous emulsification and microfluidization, sodium caseinate by microfluidization, and sucrose monopalmitate by microfluidization. All these optimized samples exhibited good storage stability for at least two weeks when stored at 4 °C or ambient temperature. The nanoemulsion stabilized with sodium caseinate was labeling friendly, and enough energy-input facilitated the achievement of small particle size around 160 nm. The chia seed oil nanoemulsion fabricated with sucrose monopalmitate could get best transparency with smallest droplet diameter (around 47 nm). Chia seed oil nanoemulsion stabilized with Tween 80 and Span 80, as one model case diluted 500× into water system, had constant transparency after fortnight's storage. Practical applications Consumers are increasingly aware of nutrition as well as sensory properties of food products. Chia seed oil is a good source of n-3 polyunsaturated fatty acids, yet difficult to be added directly into water-based liquid food or beverages. The information given in this work might be useful for designing O/W chia seed oil nanoemulsion delivery system, facilitating the further application of chia seed oil in beverages and functional food industry which required only slightly turbid or even transparent appearance.

Formulation Development and Evaluation of the Therapeutic Efficacy of Brinzolamide Containing Nanoemulsions.

Brinzolamide (BZ) is an intraocular pressure reducing agent with low bioavailability. The purpose of the present study was to overcome this issue by development of BZ containing nanoemulsions (NEs) as an ocular drug delivery system with desirable therapeutic efficacy. Brinzolamide NEs were prepared by the spontaneous emulsification method. Based on initial release studies, twelve formulations with the slowest release characteristics were subjected to further physicochemical investigations such as particle size, polydispersity index, pH, refractive index, osmolality and viscosity. The therapeutic efficacy of these formulations was assessed by measuring the intraocular pressure after instillation of the prepared NEs in normotensive albino rabbit eyes. Nanoemulsions with suitable physicochemical properties exhibited high formulation stability under different conditions. more over biological evaluations indicated that using lower drug concentrations in NE formulations (0.4%) had a similar or even better pharmacodynamic effect compared to the commercial suspension with a higher drug concentration (1%). Our findings suggest that NEs could be effectively used as carriers for enhancing the bioavailability of topically applied ophthalmic drugs.

Evaporating pure, binary and ternary droplets: thermal effects and axial symmetry breaking

The Greek aperitif Ouzo is not only famous for its specific anise-flavoured taste, but also for its ability to turn from a transparent miscible liquid to a milky-white coloured emulsion when water is added. Recently, it has been shown that this so-called Ouzo effect, i.e. the spontaneous emulsification of oil microdroplets, can also be triggered by the preferential evaporation of ethanol in an evaporating sessile Ouzo drop, leading to an amazingly rich drying process with multiple phase transitions (Tan et al., Proc. Natl Acad. Sci. USA, vol. 113 (31), 2016, pp. 8642–8647). Due to the enhanced evaporation near the contact line, the nucleation of oil droplets starts at the rim which results in an oil ring encircling the drop. Furthermore, the oil droplets are advected through the Ouzo drop by a fast solutal Marangoni flow. In this article, we investigate the evaporation of mixture droplets in more detail, by successively increasing the mixture complexity from pure water over a binary water–ethanol mixture to the ternary Ouzo mixture (water, ethanol and anise oil). In particular, axisymmetric and full three-dimensional finite element method simulations have been performed on these droplets to discuss thermal effects and the complicated flow in the droplet driven by an interplay of preferential evaporation, evaporative cooling and solutal and thermal Marangoni flow. By using image analysis techniques and micro-particle-image-velocimetry measurements, we are able to compare the numerically predicted volume evolutions and velocity fields with experimental data. The Ouzo droplet is furthermore investigated by confocal microscopy. It is shown that the oil ring predominantly emerges due to coalescence.

Anticancer Efficacy of Self-Nanoemulsifying Drug Delivery System of Sunitinib Malate.

Sunitinib malate (SM) is reported as a weakly soluble drug in water due to its poor dissolution rate and oral bioavailability. Hence, in the current study, various "self-nanoemulsifying drug delivery systems (SNEDDS)" of SM were prepared, characterized and evaluated for the enhancement of its in vitro dissolution rate and anticancer efficacy. On the basis of solubilization potential of SM in various excipients, "Lauroglycol-90 (oil), Triton-X100 (surfactant) and Transcutol-P (cosurfactant)" were selected for the preparation of SM SNEDDS. SM-loaded SNEDDS were developed by spontaneous emulsification method, characterized and evaluated for "thermodynamic stability, self-nanoemulsification efficiency, droplet size, polydispersity index (PDI), zeta potential (ZP), surface morphology, refractive index (RI), the percent of transmittance (% T) and drug release profile." In vitro dissolution rate of SM was significantly enhanced from an optimized SNEDDS in comparison with SM suspension. The optimized SNEDDS of SM with droplet size of 42.3nm, PDI value of 0.174, ZP value of -36.4mV, RI value of 1.339, % T value of 97.3%, and drug release profile of 95.4% (after 24h via dialysis membrane) was selected for in vitro anticancer efficacy in human colon cancer cells (HT-29) by MTT assay. MTT assay indicated significant anticancer efficacy of optimized SM SNEDDS against HT-29 cells in comparison with free SM. The results of this study showed the great potential of SNEDDS in the enhancement of in vitro dissolution rate and anticancer efficacy of poorly soluble drug such as SM.

Cinnamon oil nanoemulsions by spontaneous emulsification: Formulation, characterization and antimicrobial activity

The goal of this study was to formulate stable cinnamon oil nanoemulsions (NEs) exhibiting high antimicrobial activity by using the low-energy approach: spontaneous emulsification (SE) and compare it with two high-energy methods. To prepare the nanoemulsions by SE, oil phase containing cinnamon oil (CO) and carrier oil (coconut oil (CNO)) at different ratios (2:8–10:0) and surfactant (Tween 80) at 10% (w/w) was titrated into an aqueous phase (distilled water). For antimicrobial activity, agar disc diffusion method with E. coli as the model microorganism was used. NEs were characterized by Dynamic Light Scattering (DLS) and Transmission Electron Microscopy (TEM). Both DLS and TEM gave parallel results and mean particle size were found as ∼ 100 nm for 6:4 (CO: CNO) oil phase composition. These NEs also showed high physical stability during one-month storage. NEs were also prepared by using two high-energy homogenization methods: microfluidization and ultrasonication. Ultrasonication and SE showed similar trends for mean particle size and microbial activity. Microfluidization resulted in the smallest mean particle size (p < 0.05) and antimicrobial activity was not effected from cinnamon oil concentration (p > 0.05).

Self-Propelled Motion of Monodisperse Underwater Oil Droplets Formed by a Microfluidic Device.

We evaluated the speed profile of self-propelled underwater oil droplets comprising a hydrophobic aldehyde derivative in terms of their diameter and the surrounding surfactant concentration using a microfluidic device. We found that the speed of the oil droplets is dependent on not only the surfactant concentration but also the droplet size in a certain range of the surfactant concentration. This tendency is interpreted in terms of combination of the oil and surfactant affording spontaneous emulsification in addition to the Marangoni effect.

Formulation, Characterization and Properties of Hemp Seed Oil and Its Emulsions.

The formulation, characterization, and anticipated antibacterial properties of hemp seed oil and its emulsions were investigated. The oil obtained from the seeds of Cannabis sativa L. in refined and unrefined form was characterized using iodine, saponification, acid values, and gas chromatography, and was employed for the preparation of stable oil-in-water emulsions. The emulsions were prepared using pairs of non-ionic surfactants (Tween, Span). The effects of the emulsification method (spontaneous emulsification vs. high-intensity stirring), hydrophilic lipophilic balance (HLB), type and concentration of surfactant, and oil type on the size and distribution of the emulsion particles were investigated. It was found that the ability to form stable emulsions with small, initial particle sizes is primarily dependent on the given method of preparation and the HLB value. The most efficient method of emulsification that afforded the best emulsions with the smallest particles (151 ± 1 nm) comprised the high-energy method, and emulsions stable over the long-term were observed at HBL 9 with 10 wt % concentration of surfactants. Under high-intensity emulsification, refined and unrefined oils performed similarly. The oils as well as their emulsions were tested against the growth of selected bacteria using the disk diffusion and broth microdilution methods. The antibacterial effect of hemp seed oil was documented against Micrococcus luteus and Staphylococcus aureus subsp. aureus. The formulated emulsions did not exhibit the antibacterial activity that had been anticipated.

Utilisation of spontaneous emulsification to fabricate lutein‐loaded nanoemulsion‐based delivery systems: factors influencing particle size and colour

SummaryFactors influencing the formation and properties of lutein‐loaded nanoemulsions fabricated using spontaneous emulsification (SE) were investigated. Nanoemulsion formation depended on oil type: small droplets (diameter ≈ 200 nm) with a narrow monomodal particle size distribution (polydispersity index ≈ 0.23) could be formed using medium‐chain triglycerides (MCT), but not long‐chain triglycerides. Nanoemulsion formation also depended on surfactant type and concentration, with Tween 80 being the most effective surfactant. Optimisation of lutein‐loaded nanoemulsions formed by SE led to systems with a final composition of 10 wt% oil phase (0.12 wt% lutein + 9.88 wt% MCT), 10 wt% Tween 80, and 80 wt% aqueous phase. The nanoemulsions were stable to droplet aggregation when stored at ambient temperature for up to 1 month; however, some colour fading occurred due to lutein degradation. This study indicated the potential of nanoemulsion‐based delivery system fabricated using a low‐energy method for encapsulation and protection of lutein.

Core–Shell Structure Formation from Droplets by Droplet Shrinkage and Spontaneous Emulsification

This paper describes a novel method for preparing core–shell structures from droplets. The core–shell structures are formed via water transfer from a droplet of polymer solution to a high-osmotic-p...

Thymol nanoemulsions formed via spontaneous emulsification: Physical and antimicrobial properties

In this work, we prepared various sub-micron thymol emulsions with high hydrophilic-lipophilic balance (HLB) surfactants via spontaneous emulsification. Emulsion properties, such as size, polydispersity and charge, were assessed for each surfactant type and mass fraction. Emulsion stability was characterized by monitoring droplet size following exposure to physical (centrifugation) and thermal stressors (freeze, thaw cycling). Emulsions were subsequently screened against several challenge pathogens to evaluate antimicrobial efficacy. Based on these time-kill assays, exemplary formulations were further tested as sanitizing washes on lettuce and blueberries inoculated with food-borne bacterial biofilms. Antimicrobial data elucidate both surfactant and formulation specific antagonisms between thymol and the emulsifying agents. However, the best emulsion compositions were capable of reducing planktonic bacteria by >4 logs and biofilm bacteria by 1.5–2.5 logs in 60 s. These results are comparable to the efficacy of chlorine at ∼50–200ppm. The experimental results have implications in emulsion formulations involving thymol and other terpenoids.

Impact of oil composition on formation and stability of emulsions produced by spontaneous emulsification

ABSTRACTIn this study, triglycerides of different chain lengths were mixed with paraffin oil, and their effectiveness in forming emulsions produced by spontaneous emulsification upon the addition of water was investigated. The emulsion droplet size exhibited a similar trend as a function of the triglyceride/paraffin oil composition for medium-chain (MCTs) (C8–C10) and long-chain (C18) triglycerides (LCTs). However, emulsions formulated with MCTs and LCTs have a much smaller droplet size (about 50 nm) than emulsions based upon short-chain (C4) triglycerides (SCTs). The addition of SCTs resulted in droplet sizes around 800 nm and the emulsions formed were very unstable. The droplet size, polydispersity index, zeta potential, and emulsion stability of these systems will be described as a function of the oil phase composition.

The antioxidant, antibacterial, antibiofilm activity of essential oil from Citrus medica L. var. sarcodactylis and its nanoemulsion

In this work, the nanoemulsion of essential oil from Citrus medica L. var. sarcodactylis was prepared using a spontaneous emulsification method. Meanwhile, the effect of nanoemulsification on the antioxidant, antibacterial and antibiofilm activity of essential oil was evaluated. GC–MS analysis indicated nineteen compounds in the essential oil, and the essential oil was dominated by d-Limonene (50.04%). The minimum and stable droplets (73 nm) of essential oil nanoemulsion were formulated when the concentration of essential oil in oil phase was 50% (w/w). The hydroxyl radicals, DPPH radicals scavenging ability, iron reducing power, antibacterial and antibiofilm activity of nanoemulsified essential oil were significantly higher than those of pure essential oil at same concentration. Moreover, the nanoemulsified essential oil exhibited higher inhibitive effect on the bacteria in tofu than pure essential oil. Therefore, nanoemulsification significantly enhanced the antioxidant, antibacterial and antibiofilm activity/efficiency of essential oils, which will promote the abroad utilization of essential oils.

A novel ionic amphiphilic chitosan derivative as a stabilizer of nanoemulsions: Improvement of antimicrobial activity of Cymbopogon citratus essential oil

Amphiphilic chitosans have been recently proposed to improve delivery of poorly soluble drugs. In the present paper a derivative obtained by ionic interaction between chitosan and oleic acid was for the first time studied to physically stabilize o/w nanoemulsions of an antimicrobial essential oil, Cymbopogon citratus (Lemongrass), in a low energy and mild conditions emulsification process.The novel combination of spontaneous emulsification process with chitosan oleate amphiphilic properties resulted in a stable dispersion of a few hundred nanometer droplets. Positive zeta potential confirmed the presence of a chitosan shell around the oil droplets, which is responsible for the nanoemulsion physical stabilization and for the maintenance of chitosan bioactive properties, such as mucoadhesion. Cytotoxicity test was performed on four different cell lines (HEp-2, Caco-2, WKD and McCoy cells) showing biocompatibility of the system. The maintenance and in some cases even a clear improvement in the essential oil antimicrobial activity towards nine bacterial and ten fungal strains, all of clinical relevance was verified for Lemongrass nanoemulsion.

Spontaneous emulsification and self-propulsion of oil droplets induced by the synthesis of amino acid-based surfactants.

It is well known that oil droplets in or on water exhibit spontaneous movement induced by surfactants, and this self-propulsion is regarded as an important factor in droplet-based models for a living cell. We report here an oil-droplet system spontaneously producing amino acid-based surfactants, which are then utilized for the droplets' self-propulsion. Thus this system is an active system capable of producing the fuel for the propulsion by itself, which can be used as a conceptual model for cell metabolism.

Critical physicochemical and biological attributes of nanoemulsions for pulmonary delivery of rifampicin by nebulization technique in tuberculosis treatment

The study investigated aerosolization, pulmonary inhalation, intracellular trafficking potential in macrophages and pharmacokinetics profiles of rifampicin-oleic acid first-generation nanoemulsion and its respective chitosan- and chitosan-folate conjugate-decorated second and third-generation nanoemulsions, delivered via nebulization technique. The nanoemulsions were prepared by conjugate synthesis and spontaneous emulsification techniques. They were subjected to physicochemical, drug release, aerosolization, inhalation, cell culture and pharmacokinetics analysis. The nanoemulsions had average droplet sizes of 40–60 nm, with narrow polydispersity indices. They exhibited desirable pH, surface tension, viscosity, refractive index, density and viscosity attributes for pulmonary rifampicin administration. All nanoemulsions demonstrated more than 95% aerosol output and inhalation efficiency greater than 75%. The aerosol output, aerosolized and inhaled fine particle fractions were primarily governed by the size and surface tension of nanoemulsions in an inverse relationship. The nanoemulsions were found to be safe with third-generation nanoemulsion exhibiting higher cell internalization potential, reduced plasma drug concentration, and higher lung drug content.

Artesunate Loaded Self Nanoemulsified Drug Delivery System: A Preliminary Study for Improved Efficacy in the Treatment of Malaria: Formulation, Characterization and Bio-Distribution Study

The current study focused on formulation and evaluation of Artesunate loaded Self Nanoemulsified Drug Delivery System (SNEDDS). The research oriented towards the establishment of the pharmacokinetic parameters and biodistribution of Artesunate for SNEDDS. Artesunate nanoemulsion were developed using lipid, surfactant and Co Surfactant respectively (Capryol 90, Cremophor EL and Ethanol) by Spontaneous emulsification method. The investigation includes various characterization studies viz., particle size distribution, poly dispersibility index, zeta potential, viscosity, refractive index, % transmission and conductivity. The results were found to be 110.4 nm, 0.386, -36.6 mV, 19.54 cps, 1.287, 100, 367.2 μS/cm respectively with the optimized formulation 5. The in vitro drug release of Artesunate from SNEDDS formulation for was extremely significant when compared to pure drug suspension and the marketed formulation. The maximum release of drug from SNEDDS, marketed formulation and pure drug suspension was 98.78%, 62.78% and 20.88% respectively. The pharmacokinetic parameters of Cmax, AUC(0- 2 h), AUC(0-∞), Kel, Tmax and MRT were found to be 2467 ± 11.98 ng/ml, 1278 ± 0.18 h.ng/ml, 3278 ± 0.78 h.ng/ml, 1.04 ± 0.07 h-1, 1.0 h and 1.87 ± 0.01 h, respectively. From biodistribution studies the concentration of dihydroartemisinin (metabolite of Artesunate) was found to be maximum in the order of liver>lung>kidney>spleen>brain>heart. The highest concentration of 1951.8 ng/g was found to be in the liver.