Formation of Concentrated Nanoemulsions by Extreme Shear

Abstract

We have systematically investigated the production of “nanoemulsions,” droplets of one liquid phase in another immiscible liquid phase that have diameters less than 100 nm. Our approach relies on a combination of extreme shear due to multipass, high‐pressure microfluidic injection and systematic control of the emulsion's composition. By repeatedly shearing a silicone oil‐in‐water emulsion in an inhomogeneous extensional shear flow, the multipass approach enables us to reduce the droplet polydispersity and average radius. Using dynamic light scattering, we study the changes in the average radius, ?a?, as a function of the number of passes, driving injection pressure (i.e., shear rate), droplet volume fraction, surfactant concentration, and droplet oil viscosity. The smallest nanoemulsion that we obtain has ?a?=18 nm. At large droplet volume fractions φ≥0.65, we observe phase inversion, rather than a reduction in the droplet size. This provides evidence that droplet coalescence can occur during extreme shear, even when a significant excess of a strongly stabilizing surfactant is present.     

Synthesis of low-melting-point metallic nanoparticles with an ultrasonic nanoemulsion method

A one-step, economical nanoemulsion method has been introduced to synthesize low-melting-point metallic nanoparticles. This nanoemulsion technique exploits the extremely high shear rates generated by the ultrasonic agitation and the relatively large viscosity of the continuous phase - polyalphaolefin (PAO), to rupture the molten metal down to diameter below 100 nm. Field’s metal nanoparticles and Indium nanoparticles of respective average diameters of 15 nm and 30 nm have been obtained. The nanoparticles size and shape are determined by transmission electron microscopy (TEM). Their phase transition behavior is examined using a differential scanning calorimeter (DSC). It is found that these nanoparticles dispersed in PAO can undergo reversible, melting-freezing phase transition, and exhibit a relatively large hysteresis. The experimental results suggest that the nanoemulsion method is a viable route for mass production of low-melting nanoparticles.     

Block copolymers at interfaces: Interactions with physiological media

Triblock copolymers (also known as Pluronics or poloxamers) are biocompatible molecules composed of hydrophobic and hydrophilic blocks with different lengths. They have received much attention recently owing to their applicability for targeted delivery of hydrophobic compounds. Their unique molecular structure facilitates the formation of dynamic aggregates which are able to transport lipid soluble compounds. However, these structures can be unstable and tend to solubilize within the blood stream. The use of nanoemulsions as carriers for the lipid soluble compounds appears as a new alternative with improved protection against physiological media. The interfacial behavior of block copolymers is directly related to their peculiar molecular structure and further knowledge could provide a rational use in the design of poloxamer-stabilized nanoemulsions. This review aims to combine the new insights gained recently into the interfacial properties of block copolymers and their performance in nanoemulsions. Direct studies dealing with the interactions with physiological media are also reviewed in order to address issues relating metabolism degradation profiles. A better understanding of the physico-chemical and interfacial properties of block copolymers will allow their manipulation to modulate lipolysis, hence allowing the rational design of nanocarriers with efficient controlled release.     

Self-emulsification in chemical and pharmaceutical technologies

The interest in the low energy self-emulsification techniques has exploded in the recent years, driven by three main trends: by the transition to “greener” technologies in both its aspects—less energy consumption and replacement of the petrochemicals by natural ingredients; by the costly and maintenance demanding equipment for nanoemulsification; and by the quest for efficient and robust self-emulsifying formulations for oral drug delivery. Here, we first present a brief overview of the main known low-energy methods for nanoemulsion formation, focusing on their mechanistic understanding and discussing some recent advances in their development and applications. Next, we review three conceptually new approaches for self-emulsification in chemical technologies, discovered in the last several years. The colloidal features and the specific requirements of the self-emulsifying drug-delivery systems (SEDDS) are also discussed briefly. Finally, we summarize the current trends and the main challenges in this vivid research area.     

Synergistic antibacterial effects of ultrasound and thyme essential oils nanoemulsion against Escherichia coli O157:H7

Essential oil nanoemulsions have been proven to have stronger antimicrobial effects compared to the essential oil alone or coarse emulsion. Sonoporation could be the promising candidate to trigger a synergistic effect with thyme essential oil nanoemulsion (TEON) and produce a more effective antibacterial efficacy. Therefore, in this study, the bactericidal effects of ultrasound (US) in combination with TEON treatments against Escherichia coli (E. coli) O157:H7 were investigated. The remarkable synergistic effects of US (20 kHz, 255 W/cm², 9 min) and TEON (0.375 mg/mL) treatments at 22 °C reduced E. coli O157:H7 populations by 7.42 ± 0.27 log CFU/mL.The morphological changes of cells exposed to different treatments were observed by scanning electron microscopy and transmission electron microscopy. The results showed that the synergistic effects of the ultrasound and TEON treatments altered the morphology and interior microstructure of organism cells. Laser scanning confocal microscopy (LSCM) images revealed that the combination treatments of ultrasound and TEON altered the permeability of cell membranes, and this affected the integrity of E. coli O157:H7 cells. This was further indicated by the high amounts of nucleic acids and proteins released from these cells following treatment.The results from this study illustrated the mechanisms of the synergistic effects of sonoporation and TEON treatments and provided valuable information for their potential in food pasteurization.     

Nanostructure-Driven Indocyanine Green Dimerization Generates Ultra-Stable Phototheranostics Nanoparticles

Indocyanine green (ICG) is the only near-infrared (NIR) dye approved for clinical use. Despite its versatility in photonic applications and potential for photothermal therapy, its photobleaching hinders its application. Here we discovered a nanostructure of dimeric ICG (Nano-dICG) generated by using ICG to stabilize nanoemulsions, after which ICG enabled complete dimerization on the nanoemulsion shell, followed by J-aggregation of ICG-dimer, resulting in a narrow, red-shifted (780 nm→894 nm) and intense (≈2-fold) absorbance. Compared to ICG, Nano-dICG demonstrated superior photothermal conversion (2-fold higher), significantly reduced photodegradation (−9.6 % vs. −46.3 %), and undiminished photothermal effect (7 vs. 2 cycles) under repeated irradiations, in addition to excellent colloidal and structural stabilities. Following intravenous injection, Nano-dICG enabled real-time tracking of its delivery to mouse tumors within 24 h by photoacoustic imaging at NIR wavelength (890 nm) distinct from the endogenous signal to guide effective photothermal therapy. The unprecedented finding of nanostructure-driven ICG dimerization leads to an ultra-stable phototheranostic platform.     

Ultrasonic emulsification of parenteral valproic acid-loaded nanoemulsion with response surface methodology and evaluation of its stability

Response surface methodology (RSM) was used to optimize the formulation of a nanoemulsion for central delivery following parenteral administration. A mixture of medium-chain triglyceride (MCT) and safflower seed oil (SSO) was determined as a sole phase from the emulsification properties. Similarly, a natural surfactant (lecithin) and non-ionic surfactant (Tween 80) (ratio 1:2) were used in the formulation. A central composite design (CCD) with three-factor at five-levels was used to optimize the processing method of high energy ultrasonicator. Effects of pre-sonication ultrasonic intensity (A), sonication time (B), and temperature (C) were studied on the preparation of nanoemulsion loaded with valproic acid. Influence of the aforementioned specifically the effects of the ultrasonic processing parameters on droplet size and polydispersity index were investigated. From the analysis, it was found that the interaction between ultrasonic intensity and sonication time was the most influential factor on the droplet size of nanoemulsion formulated. Ultrasonic intensity (A) significantly affects the polydispersity index value. With this optimization method, a favorable droplet size of a nanoemulsion with reasonable polydispersity index was able to be formulated within a short sonication time. A valproic acid loaded nanoemulsion can be obtained with 60% power intensity for 15 min at 60 °C. Droplet size of 43.21 ± 0.11 nm with polydispersity index of 0.211 were produced. The drug content was then increased to 1.5%. Stability study of nanoemulsion containing 1.5% of valproic acid had a good stability as there are no significant changes in physicochemical aspects such as droplet size and polydispersity index. With the characteristisation study of pH, viscosity, transmission electron microscope (TEM) and stability assessment study the formulated nanoemulsion has the potential to penetrate blood–brain barrier in the treatment of epilepsy.     

香茅油纳米乳剂的构建、表征、抗菌性能和细胞毒性

化学合成杀菌剂的大量、不合理使用对人类健康造成危害的同时也会导致严重的环境污染。因此,迫切需要寻找低毒、高效、无残留的天然杀菌剂。植物精油因其优良的杀菌活性、良好的生物相容性和丰富的来源,已成为农业病害防控领域的研究热点。香茅油是一种具有趋避、杀虫和抗菌活性的天然植物精油,主要包括香茅醛、香叶醇和香茅醇。目前,关于香茅油的研究主要集中于卫生害虫的驱避和防治,而用于农业致病菌防治的相关报道相对较少。在实际应用中,香茅油的疏水性和挥发性导致其生物利用度低,不能充分发挥生物活性。因此,构建一种改善香茅油疏水性、降低挥发性的递送系统十分必要。纳米乳剂因具有液滴细微均匀、物理稳定性好、渗透能力强以及生物利用度高等优点,已成为疏水农药的重要递送系统。本研究通过观察样品的外观和微观结构,并且测量样品液滴大小,考察了乳化剂种类(亲水亲油平衡值,HLB)、用量和乳化时间对纳米乳剂形成及稳定的影响,在此基础上筛选了香茅油纳米乳剂的优化配方。同时本研究还调查了香茅油纳米乳剂的生物活性和生物安全性。结果表明,以蓖麻油聚氧乙烯醚EL-40 (HLB = 13.5)为乳化剂的纳米乳剂性能最佳,且乳化剂用量从3%增加到7% (w,质量分数)时,纳米乳剂稳定性提高。此外,高速剪切3 min获得的纳米乳剂稳定性最高。基于此,确定了香茅油纳米乳剂的优化配方为：5% (w)香茅油,6% (w)乳化剂(EL-40),89% (w)去离子水,高速剪切3 min。香茅油纳米乳剂对菠萝泛菌(Pantoea ananatis)具有良好的抑制作用,抑制中浓度(EC₅₀)为74.85 mg·L⁻¹。纳米乳剂(低于100 mg·L⁻¹)处理人体正常肝细胞(L02) 24 h后,细胞存活率仍高于83%,凋亡率仅为6.93%,表明香茅油纳米乳剂具有较低的细胞毒性。本研究有助于设计和构建稳定、高效、安全的农业纳米乳剂,同时为植物精油作为农业杀菌剂提供了切实可行的解决方案。     

Ultrasound assisted formation of essential oil nanoemulsions: Emerging alternative for Culex pipiens pipiens Say (Diptera: Culicidae) and Plodia interpunctella Hübner (Lepidoptera: Pyralidae) management

Over the last years, nanotechnology has contributed to the development of new botanical insecticides formulations based on essential oils (EO), which are safe for the human health and the environment. Nanoemulsions (NEs) can enhance the bioactivity of the EO to prevent the premature volatility and degradation of the active ingredients. In our work, geranium EO (Geranium maculatum L.) was used to develop micro and nanoemulsions adding Tween 80 as surfactant. For NEs formulation, ultrasound was applied and the physicochemical and ultrasound parameters were optimized: oil: surfactant ratio = 1:2, ultrasound power = 65 W, sonication time = 2 min, cycles = 30 on/20 off and ultrasonic probe distance = 3.7 cm. The NEs obtained had 13.58 nm and polydisperse index (PDI) values of 0.069. They were stored at 25 °C and were stable for 60 days.The present study also demonstrated the potential of NEs to enhance the toxicity of geranium EO against larvae of Culex pipiens pipiens (EO LC₅₀ = 80.97 ppm, NEs LC₅₀ = 48.27 ppm) and Plodia interpunctella (EO + β-cypermethrin LD₅₀ = 0.16 μg larvae⁻¹, NEs + β-cypermethrin LD₅₀ = 0.07 μg larvae⁻¹). Overall, our findings pointed out that NEs can increase twofold the insecticidal efficacy of EO, and thus, they can be considered further for the development of botanical insecticides.     

Development of nanoformulation for hyperpigmentation disorders: Experimental evaluations,in vitro efficacy and in silico molecular docking studies

Hyperpigmentation is a crucial dermatological disorder. This study aims to formulate a nanoemulsion formulation containing chlorogenic acid (CA) for hyperpigmentation treatment, to carry out characterization studies, and to investigate its efficacy and safety in vitro and in silico analysis.In line with this purpose, CA nanoemulsions (CA-NEs) were developed using the ultrasonic homogenization method. Accelerated stability tests were performed to examine the kinetic and thermodynamic stability of the CA-NEs to ascertain the presence of any stability issues. After the heating–cooling test, appropriate CA-NEs were stored for 60 days in three different stability environments to examine the physicochemical stability and determine the finalized formulation. The toxicity of the finalized CA-NE formulation was evaluated by genotoxicity/mutagenicity and cytotoxicity tests. The tyrosinase and melanogenesis activities of the finalized CA-NE formulation were determined on the Melanoma B16F0 cell line. Finally, the molecular docking method was used to reveal interactions of CA that play an essential role in tyrosinase inhibition. Additionally, the mushroom and human tyrosinase enzymes were used to determine the activity of CA. In addition, the comparison study with the molecular docking method was carried out using kojic acid as a reference molecule.In conclusion, the molecular docking study, pharmacokinetic analyses, and in vitro studies showed that F4P1 coded CA-NE formulation might hold promise as an innovative formulation in cosmetic applications such as skin-lightening effects with its high efficacy and safety profile.