Low-energy Emulsification Research Articles

PH-shifting treatment improved the emulsifying ability of gelatin under low-energy emulsification

The effects of pH-shifting treatments (pH 3, 5, 7, 9, and 11) on the stability of gelatin emulsions made by low-energy stirring were investigated. pH-shifting treatments significantly enhanced the ESI and EAI of the emulsion (P < 0.05) and reduced its particle size (P < 0.05) under low-energy emulsifying conditions. The pH11–7 shifting treatment significantly increased the degree of depolymerization and the level of ordered structure of gelatin (P < 0.05). These transformations resulted in a significant increase in the exposure of hydrophobic and negatively charged residues (P < 0.05) on the surface of gelatin, facilitating a faster adsorption rate of gelatin onto the oil-water interface as well as an increase in the amount of gelatin adsorbed at the interface. Moreover, the alkali-shifting treatment promoted the formation of a thin viscoelastic interfacial film, which contributed to the enhanced stability of the emulsion.

The synergistic effect of α-tocopherol and phloretin-loaded nanoemulsions on improvement of the stability, antioxidant, and tyrosinase inhibitory potentiality.

The purpose of this study was to prepare and evaluate the formulation of nanoemulsions (NEs) to encapsulate phloretin (PT) to improve its stability, antioxidant, and tyrosinase inhibitory competence. The aim of this study was to improve the stability, antioxidant, and tyrosinase inhibitory effects of PT via NEs. The formulations were prepared using low energy emulsification method for PT-VE-NEs, α-tocopherol (Vitamin E) and medium chain triglycerides (MCT) were used as the oil phase, and Tween 60 was used as the emulsifier and PEG-400 as the co-emulsifier. The droplet size and zeta potential of oil-in-water NEs were evaluated using dynamic light scattering. The PT-VE-NEs were also characterized by transmission electron microscopy and Fourier transform infrared spectroscopy. The mean droplet diameter was 14.85±0.14nm, with a zeta potential of -2.47±0.51mV. Fourier transform infrared spectroscopy revealed the formation of molecular interactions in the NEs formulations. PT-VE-NEs size was maintained the same during the in vitro digestion study. The particle size of PT-VE-NE remained stable during in vitro digestion. The addition of VE significantly improved the antioxidant, tyrosinase inhibitory effects, as well as thelion and physical stability of PT-VE-NE. The results revealed that NEs is a promising strategy to improve the functionality and stability of PT and VE. PT-VE-NEs will be applied for the preservation of fruits.

Formulation, characterization, and stability of morin hydrate-loaded nanoemulsion

Morin hydrate (MH) is a bioflavonoid belonging to flavonol class. Despite its pharmacological activities, MH has inherent low aqueous solubility and chemical instability hindering biological applications of this flavonol. In this regard, this study aimed to develop and characterize nanoemulsion containing MH. Nanoemulsion formulations were prepared using phase inversion temperature method and characterized by size, polydispersity index (PdI), physical stability, AFM analysis, incorporation efficiency (IE), and in vitro release. Following the formulation design, F10 formulation was chosen to incorporate MH. Nanoemulsion containing MH (MH-NE) showed droplet size in nanometric scale (< 100 nm) with homogeneous size distribution (PdI < 0.1). In addition, good physical stability of MH-NE was demonstrated using analytical photocentrifugation method where the light transmission profiles did not change throughout the emulsions. According to AFM analysis, oil droplets were mostly spherical or semi-spherical having sizes uniformly distributed. The IE of MH into nanoemulsion was approximately 100%, and in vitro release profile of this flavonol from formulation was gradual throughout the experiment. Therefore, using a reproducible method of low energy emulsification we developed a stable colloidal dispersion of nanoemulsion containing MH.

Application of the Simplex Lattice Design Method to Determine the Optimal Formula of Diclofenac Sodium Nanoemulsion

Background: The success of nanoemulsion preparation, with the aim of producing good characteristic values, is determined by the ratio of each component. The design of experiments (DoE) approach using the Simplex Lattice Design (SLD) method can be used to determine the optimal formula for nanoemulsions, with variable factors consisting of oleic acid, Tween 20:ethanol (4:1), and water. The observed response variables included droplet size, PDI, and pH. Objective: DoE can help reduce the energy, cost, and time needed to make the optimal formula for diclofenac sodium nanoemulsions. Methods: Nanoemulsions were prepared using low-energy emulsification. Their characteristics were evaluated and analyzed using Design Expert software. Results: The optimal nanoemulsion formulation consisted of 4.17% oleic acid, 37.5% emulsifier (Tween 20: ethanol, 4:1), and 58.33% water. The nanoemulsion characteristics were good, with 20.37 a droplet size, 0.42 PDI, of 4.75 pH. The observed values were not significantly different from the predicted values, and the formula could effectively trap 1% diclofenac sodium. Conclusion: The simplex lattice design method is very useful for pharmaceutical development, such as nanoemulsion optimization.

Interfacial Cooperative Assembly of Surfactants and Opposite Wettability Nanoparticles Stabilizes Water-in-Oil Emulsions at High Temperature.

Pickering emulsions have promising applications in the development of unconventional oil and gas resources. However, the high-temperature environment of the reservoir is not conducive to the stabilization of Pickering emulsions. In addition, the preparation of Pickering emulsions under low-energy emulsification and low-concentration emulsifier conditions is a difficult challenge. Here, we report a high-temperature resistant water-in-paraffin oil Pickering emulsion, which is synergistically stabilized by polyglycerol ester (PGE) and nanoparticles with opposite wettability (lipophilic silica and hydrophilic alumina). This emulsion can be prepared under mild stirring (500 rpm) conditions and can be stable at 140 °C for at least 30 days. The synergistic effects of surfactant, silicon nanoparticles (MSNPs) with different wettability, and alumina nanoparticles (AONPs) on the stability of both emulsions and water-oil interfacial membranes were investigated through bottle experiments, cryogenic scanning electron microscopy (cryo-SEM), optical microscopy, fluorescence microscopy, etc. The results showed that both hydrophobic MSNPs and hydrophilic AONPs are adsorbed together at the water-oil interface to stabilize the W/O emulsion, which can be prepared by 500 rpm stirring. The stability of emulsions strongly depends on the wettability of MSNPs, and the MSNP with moderate hydrophobicity (for example, aqueous phase contact angle of 136°) makes the emulsion exhibit the highest stability against aggregation and settling at elevated temperatures. The emulsion stabilization mechanism was revealed in terms of the adsorption capacity of the surfactant by MSNPs, the adsorption morphology and desorption energy of nanoparticles at the water-oil interface adsorption layer, and emulsion rheology. These findings demonstrate a novel and simple strategy to prepare Pickering W/O emulsions with high-temperature stability at low shear strength.

Enhancing the efficacy of fluconazole against Leishmania major: Formulation and evaluation of FLZ-nanoemulsions for topical delivery

BackgroundCutaneous Leishmaniasis (CL) remains a significant public health concern, particularly in the tropical and subtropical regions. Present treatment options for CL such as Fluconazole (FLZ) face limitations, including low solubility and bioavailability. This study aimed to address these challenges by investigating the use of nano-emulsions (NEs) to enhance the efficacy of FLZ against Leishmania major(L.major). Materials and methodsFLZ-NEs were formulated with oleic acid, Tween-20, and ethanol using low-energy emulsification at various surfactant/co-surfactant ratios. Subsequently, a comprehensive analysis was conducted to assess the physicochemical characteristics of the samples. This analysis encompassed stability, zeta potential, pH, viscosity, refractive index, and droplet size. We then studied the anti-parasitic properties of these optimized FLZ-NEs both in vitro and in vivo. ResultsThe selected nano-emulsion (NE) formulation (2 % oleic acid, 20 % Tween 20, 10 % ethyl alcohol) showcased desirable properties like small droplet size (10.51 ± 0.24 nm), low dispersity (0.19 ± 0.03), and zeta potential value (- 0.41 ± 0.17 mV), key for stability and targeted drug delivery. This optimal formulation translated into remarkable efficacy. In vitro, FLZ-NEs demonstrated a threefold increase in their ability to combat promastigotes and a remarkable thirtyfold increase in their ability to combat amastigotes. Additionally, they demonstrated a ninefold advantage in their ability to specifically target parasites within infected macrophages, thereby attacking the infection site. These promising in vitro results translated into improved outcomes in vivo. Compared to other chemicals studied, FLZ-NE-treated mice showed decreased disease severity, weight growth, and quicker ulcer healing. It was further supported by histopathological research, which showed reduced tissue damage linked to Leishmania infection. ConclusionThese findings show the potential of nanotechnology-based drug delivery in improving anti-leishmanial treatment.

Engineering ternary systems as non-viral vehicles for transporting floxuridine oligomer

The objective of this study is to evaluate the potential applicability of a ternary drug delivery system, that incorporates chitosan (CHI) into poly(lactic-co-glycolic) acid PLGA nanoparticles (NPs) and Floxouridine (FdU) oligomers with varying lengths to be delivered in cancer cells. Two FdU oligomers containing five (FdU5) and ten (FdU10) residues were used. PLGA NPs were prepared from O/W nano-emulsion templates using the low energy emulsification phase inversion composition (PIC) method. Binary vectors comprised of FdU oligomer/CHI and ternary vectors based on FdU/CHI/PLGA NPs were prepared and fully characterized in terms of size, surface charge, and morphology. The resultant ternary vectors displayed spherical morphology and positive surface charge, with particle sizes in the nanometric range at appropriate FdU5/CHI/PLGA and FdU10/CHI/PLGA ratios. The presence of CHI and FdU10 oligomer in the ternary system significantly reduced the cellular viability leading to greater cytotoxicity values (ca. 60 %) when compared to an unbound FdU10 oligomer. The potential of nano-emulsions as a tool for preparing ternary drug delivery systems and improving the transportation of FdU oligomers into tumor cells is highlighted in this study.

Innovative insights into the preparation of tamarind gum base film loaded with pomelo essential oil via a low-energy emulsion method combined with melatonin: Maximizing the dual functions of tamarind gum

Pomelo essential oil has good antioxidant and antimicrobial properties. The objective of this study was to modify the active packaging loaded with essential oil through low-energy emulsification, in order to achieve both film-forming and emulsifying properties of tamarind gum, and to investigate the surface activity of melatonin in the emulsion. When α:β mixing ratio of 60:40, the resulting film solution exhibited favorable apparent viscosity and reduced emulsion flocculation and precipitation phenomena. Particle size distribution analysis and optical microscopy results demonstrated that the obtained emulsion was uniformly dispersed at an α:β mixing ratio of 60:40, with droplet diameters mainly concentrated within the range of 1–100 μm. After undergoing film-forming treatment, E-3-F (α:β mixing ratio of 60:40) exhibited a smoother and more compact microstructure, leading to significant improvements in mechanical properties and barrier performance. Laser confocal microscopy imaging revealed that the addition of melatonin further reduced interfacial tension between oil and water, while simultaneously weakening hydrophobic interaction forces among oil droplets, thereby effectively inhibiting droplet aggregation behavior. Moreover, incorporation of melatonin also enhanced material compactness and imparted excellent antioxidant effects to the packaging material. Consequently, this study ultimately unveils potential for low-energy emulsification combined with melatonin application in bio-based packaging field while providing novel insights into developing multifunctional bio-based packaging.

Doxycycline monohydrate and azelaic acid Co-loaded nanoemulgel for the treatment of facial rosacea: In vitro and In vivo evaluation

Nanoemulgel have gained importance as topical delivery systems because of their potential to incorporate hydrophilic and lipophilic drugs simultaneously like emulsions and improved stability and spreadability like gels. Therefore, the current research was aimed to prepare, optimize, and evaluate the combined therapeutic efficacy of doxycycline monohydrate (DOX.H2O) and azelaic acid (AZL) loaded into a nanoemulgel (NE) against facial rosacea. The nanoemulsion was prepared via phase inversion low energy emulsification method by solubilizing DOX.H2O in peppermint oil and AZL in deionized water. The formulation was optimized using Design Expert 13. The optimized nanoemulsion has a particle size of 210.6 nm, a PDI of 0.234 and a zeta potential of −15.1 mV. SEM observations revealed the spherical morphology of oil globules, whereas FTIR results confirmed that no chemical interaction among the ingredients took place. The in vitro release study showed the burst release of 82.1 % AZL and 48.1 % release of DOX.H2O from the optimized DOX-AZL co-loaded NE in 6 h. The ex vivo permeation profile showed a minimum permeation of DOX.H2O and AZL across rat skin. Croton oil induced inflammation in mice ear confirmed the therapeutic efficacy of the prepared NE against facial rosacea. Considering the results obtained herein, the developed NE could enhance the safety and efficacy of the combination therapy against facial rosacea.

Surface decoration of PLGA nanoparticles enables efficient transport of floxuridine oligomers into mammalian cells

2′-deoxy-5-fluorouridine (Floxuridine, FdU) oligomers are repeated FdU residues linked to each other through phosphate groups exhibiting anticancer properties. One of the major hurdles exhibited by natural oligomers is their reduced stability and limited ability to impart cellular uptake. To overcome these drawbacks, electrostatic and covalent strategies have been used to combine oligomers with nanoparticles (NPs) to enhance stability and cellular internalization. Polymeric NPs, prepared from oil-in-water (O/W) PLGA nano-emulsions (NEs) using low-energy emulsification methods, have shown potential in many biomedical applications owing to their ability to transport drugs across cellular membranes. Carbodiimide-mediated amine coupling reaction and thiol-based Michael-type addition were used to attach FdU oligomers formed by five FdU residues (FdU5) to PLGA NPs. Colloidally stable dispersions of FdU5-decorated PLGA NPs were obtained and characterized in terms of size, surface charge, and morphology in physiological medium. Additionally, synthetic strategies were envisaged to functionalize the surface of FdU5-decorated polymeric NPs with folic acid (FA). Cell culture experiments showed that FdU5-decorated PLGA NPs were able to internalize efficiently inducing cytotoxic effect and inhibiting cell proliferation in tumor cells. These outcomes suggest the feasibility of grafting oligomeric FdU produgs in a covalent fashion into nanoscale platforms as a potential approach for cancer therapy.

Caffeine-Containing Emulsion: Influence of the HLB and Mixing Proportions, the Oil's Chemical Composition, and the Existence of Caffeine on Emulsion Properties.

This study employs a low-energy emulsification method to prepare caffeine-containing emulsions, denoted as Caf-EM. Three different oils, including coconut, sesame, and grape seed oils, are utilized along with the surfactants Span 80 and Tween 80. We investigate the influence of various factors, including (i) the hydrophilic-lipophilic balance (HLB) and surfactant ratio, (ii) the chemical composition of the oils, and (iii) the presence of caffeine, on the stability and size of emulsions. The results indicate that the HLB value and surfactant ratio are the most crucial factors affecting the emulsions' stability. The most stable Caf-EM formulation is achieved by combining mixed surfactants of Span 80 and Tween 80 with an optimal HLB value of 6.4 at a concentration of 15% (S15 to 6.4) across all oil types. This specific ratio also leads to significantly smaller emulsion droplet sizes than other ratios and is the only ratio that produces stable emulsions even without caffeine (denoted as EM). Notably, formulation S15-6.4 additionally causes a phase inversion from oil-in-water (O/W) to water-in-oil (W/O). Furthermore, the presence of caffeine in the water phase contributes to the formation of smaller and more stable emulsions. The particle size of Caf-EM is approximately 1.5 times smaller than that of EM. Regarding the oil's chemical composition, while there is a discernible trend in emulsion droplet size (coconut oil > grape seed oil > sesame oil), the differences within this sequence are insignificant, suggesting that the oil's chemical composition does not have a pronounced effect.

Use of Double Gelled Microspheres to Improve Release Control of Cinnamon-Loaded Nanoemulsions.

The use of nanoemulsions as encapsulation systems for active ingredients, such as cinnamon oil, has been studied. A surfactant based on polyoxyethylene glycerol esters from coconut/palm kernel oil has been used. The nanoemulsions were obtained by the two most commonly low-energy emulsification methods, the composition inversion phase (PIC) and the temperature inversion phase (PIT) methods. Nanoemulsions were successfully obtained by both methods, with very small droplet sizes (5-14 nm) in both cases, but a greater stability was observed when the PIT method was used. Nanoemulsions were encapsulated by external gelation using two different polysaccharides, alginate or chitosan, dissolved in the continuous phase of the nanoemulsion. Then, the nanoemulsion was dropped into a bath with a gelling agent. To improve the release control of cinnamon oil and avoid the burst effect, beads prepared with one of the polysaccharides were coated with the second polysaccharide and then gelled again. Double gelled beads were successfully obtained, the core with chitosan and the outer layer (shell) with alginate. SEM images showed the morphology of the single beads presenting high porosity. When the beads were coated, the porosity decreased because the second polysaccharide molecules covered the pre-existing pores. The smoother surface was obtained when this second layer was, in turn, gelled. The release patterns at pH = 2 and pH = 7 were studied. It was observed that the double gelled bead provided a more gradual release, but maintained approximately the same amount of final released oil. The release patterns were fitted to the Korsmeyer-Peppas model. The fitting parameters reflected the effect of the different coating layers, correlating with different diffusion mechanisms according to the bead core and shell materials.

Extraction of saponin from Gleditsia sinensis Lam and applications on natural shampoo

Synthetic shampoos that include several chemical components are available in the market. However, the safety and impact of chemical additives are under discussion, because their long-term use may result in hair dryness, scalp irritation, and hair loss. To develop a formulated shampoo as an alternative to synthetic shampoos, this study focused on fabricating a completely natural shampoo comprising Gleditsia sinensis Lam extract (GSW) and Sapindus mukurossi extract (SMW), Gleditsia polysaccharides (SP), cod skin collagen peptide (CSCP), and an essential oil. The influence of the interaction between GSW and SMW, SP, and CSCP components on the foaming performance was investigated using the Ross–Miles method, and the antioxidant activity was analyzed using free radical scavenging. The formulated shampoos were prepared using low-energy emulsification, and their surface tensions were determined using the Wilhelmy plate method. The antibacterial and antifungal activities of the shampoos were revealed by determining the minimum inhibitory and bactericidal concentrations. An interaction assay showed that GSW and SMW exhibited synergistic effects on foaming performance, and SP showed an improved foam stability of GSW. In addition, the antioxidant properties of the mixture (GSW and CSCP) exhibited cooperation. Finally, the optimal formulation of shampoo was GSW (20 wt%) and SMW (20 wt%), CSCP (0.5 wt%), and SP (2 wt%). The shampoo exhibited good foaming performance and decontamination and strong antioxidant, antibacterial, and antifungal activities.

AN OVERVIEW OF DISCRETE NANOFORMULATED FLAVONOIDS AND ITS IMPLICATION IN CANCER

The nanoformulation of phytochemical has been developed to withdraw the drawbacks of conventional phytochemical. Nanoformulations are the nanosized particles, modified in order to improve the delivery of active phytochemicals in the target, to improve bioavailability, and solubility. Early researches shows that various phytochemicals like curcumin, Hesperidin, resveratrol, ellagic acid, essential oil, Naringenin, and quercitin are highly modified to form the nanoformulated compounds to improve its bio-activities. The nanoformulated phytochemicals are syntheized by various methods such as high energy and low energy emulsification, electrostatic stabilization, emulsification/reverse salting-out, nanoprecipitation, emulsification/solvent diffusion, solvent evaporation, and multi-arm Nanoconjugates, enzyme responsive nanoconjugates, core-crosslinked nanoconjugate hydrophobic–hydrophilic nanoconjugates, and nanoconjugate-based solid dispersion. Interestingly, the encapsulation of phytochemicals with surfactants, oils, emulsifying agents, salting-out agents will promote the antioxidant, antitumor, cytotoxic agents and antimicrobial effects than a raw phytochemicals. Various studies showed that phytochemicals are nanoformulated by the nanoemulsion method are better in terms of active target drug delivery, increasing bioavailability and it also act as an effective biological and diagnosting agents. This review focus on Innovative approaches to nanoformulated phytochemicals and their biomedical applications.

Investigation of the mechanism of establishing a solid–water–oil system by metastable droplets and their application in the fabrication of polyol nanosheets for rapid boron removal

The emulsion method is a typical way for the preparation of nanomaterials, however, it usually requires a lot of energy and surfactants to form and stabilize of emulsions. A critical factor limiting its application is to control the morphology of the material by modulating the size of the emulsion droplets. In this work, a novel solid-water–oil (S-W-O) system based on the integration of metastable emulsion and salt template method was proposed, and the functionalized silica nanosheets were prepared by the one-pot method. The size of the prepared nanosheets is relatively uniform, with a length of 800 to 1200 nm and a width of about 200 nm. Subsequently, a large number of epoxy group sites were introduced into the nanosheets relying on distillation precipitation polymerization, and the polyol groups were successfully loaded. Finally, the polyol-functionalized nanosheet adsorbent (NS@GMA-NMDG) was obtained and applied for the rapid removal of boron. NS@GMA-NMDG shows favorable adsorption performance for boric acid in solution, with a maximum adsorption capacity of about 35.49 mg g−1 based on the Langmuir model fitting and a fast adsorption rate of about 30 min to reach 96.3% of the adsorption equilibrium concentration. Remarkably, the investigation of the formation mechanism of nanosheets reveals that salt plays an important role in the S-W-O system. This study not only puts forward a novel method of designing and synthesizing nanosheet adsorbents, but also the application of surfactant-free and low-energy emulsification reflects the concepts of energy saving and clean production, which provides fresh inspirations for the development of new environmentally friendly adsorbents.

Fine-tuning formulation and biological interaction of doxorubicin-loaded polymeric nanoparticles via electrolyte concentration modulation

Doxorubicin (DOX) is amongst the most widely used chemotherapeutic drugs against various cancers. However, its controlled biodistribution to the tumor site at the required pharmacokinetics profile remains challenging. In this work, a vast study of formulation parameters has been performed to control doxorubicin loading into polymeric nanoparticles in physiological conditions. Water-in-oil-in-water (W1/O/W2) template emulsions have been formulated, including doxorubicin in the internal water phase. Specifically, the system [Doxorubicin in aqueous solution (W1) / Pluronic F-127 (S) and PLGA in ethyl acetate (O)], [Polysorbate 80 (S) in water solution], using phosphate buffer on both aqueous phases at different electrolyte concentrations has been established. The first W1/O nano-emulsion was formed by high-speed homogenization, and the second O/W2 nano-emulsion was formed by the phase inversion composition method, a low-energy emulsification appropriated for pharmaceutical compounds. Although many previous studies had already used double emulsions for DOX encapsulation in nanofluids, here, for the first time, the salt concentration of the water phases has been varied to control the resulting doxorubicin and nanoparticle properties. The addition of high concentrations of electrolytes in both aqueous phases decreases the solubility and dissolution rates of the drug, leading to a high degree of DOX dimerization. This phenomenon significantly impacts the internalization and subcellular localization. Facilitating drug nuclear accumulation is of vital interest, and this is primarily achieved when doxorubicin is incorporated into nanoparticles formulated with PBS at low electrolyte concentrations (2.5 mM), which exhibit exceptional internalization properties. Thus, it has been demonstrated that doxorubicin loading in polymeric nanoparticles can be tuned by only varying salt concentrations of template W1/O/W2 emulsions. Consequently, our results show the adequacy of the double nano-emulsion templating for the generation of non-toxic DOX-loaded polymeric nanoparticles with different physicochemical properties and interaction with the cell surface that would allow their use for various anticancer therapies.

A low-energy emulsification platform based on a Diet Coke–Mentos reaction-derived bubbly flow for formulating various emulsions as drug carriers

The formulation of a drug using high-energy emulsification commonly causes drug deterioration. Exploiting the well-known Diet Coke–Mentos reaction (DCMR), a U-shaped tube reactor that can generate an eruption of bubbly flow that can serve as a low-energy emulsification platform, is proposed. The liquid in the U-tube reactor is a supersaturated solution of aqueous CO2, which mimics Diet Coke. When glass beads with rough surfaces, mimicking Mentos, are dropped into the carbonated water, an eruptive bubbly flow is spontaneously created, mediating effective emulsification at a compound water–oil interface. Experimental results demonstrate that DCMR-mediated bubbly flow may provide a versatile platform for the production of “oil-in-water” or “water-in-oil” droplets and Pickering emulsion composite particles as drug carriers. The DCMR-derived bubbly flow is generated without significant temperature elevation, so the activity of the drug to be emulsified is unaffected. In vivo results reveal the feasibility of using this low-energy emulsification platform to formulate an emulsion system that contains catalase, a temperature-sensitive oxidoreductase, to mitigate an experimentally formed paw inflammation in mice. The as-proposed emulsification platform is attractive for formulating numerous drug delivery systems on a small-scale in a customized manner to meet the needs of each individual for personalized medicine.

Simultaneous Intranasal Codelivery of Donepezil and Memantine in a Nanocolloidal Carrier: Optimization, Pharmacokinetics, and Pharmacodynamics Studies.

This work focuses on developing nanoemulsions using a low-energy emulsification method for the codelivery of donepezil and memantine in one dosage form intended to be administered via the intranasal route for enhanced brain delivery. The nanoemulsion formulation was prepared using a low emulsification technique and characterized using various microscopy and nasal ciliotoxicity studies. The safe nanoemulsion was intended for preclinical pharmacokinetics with brain distribution and pharmacodynamics in a scopolamine-induced murine model. The formulated nanoemulsion was 16 nm in size, with a zeta potential of -7.22 mV, and exhibited a spherical shape. The brain concentration of IN-administered NE for DPZ and MEM was ∼678 and 249 ng/mL after 15 min. This concentration is more than 2 times higher in amount when compared with NE administered via PO, free drug solution administered via IN and PO route both. However, the plasma concentration of IN-administered NE for DPZ and MEM was ∼3 and 28 ng/mL after 15 min. In pharmacodynamic studies, the efficacy of NE administered via the IN route was higher when compared with other groups in neurobehavioral, biochemical estimation, and gene expression studies. The results suggest that the IN route can be explored in the future for the delivery of actives via nanocolloidal carriers in the brain for neurological disorders and can serve as promising alternatives for conventional dosage forms and routes.

Improvement of hydrolysis efficiency and interfacial properties of zein using nanoemulsions prepared by a low energy emulsification method

Alcalase hydrolysis can improve the interfacial properties and functional features of proteins. It usually reacts in water. However, zein is difficult to dissolve in water due to its amino acid composition, which greatly limits its application in food industry. To achieve heterogeneous hydrolysis of zein, a new and stable reaction system which called bicontinuous microemulsion was constructed. It consisted of Tween-80, absolute ethanol, n-octanol and distilled water. The average particle size of the nanoemulsion system was 18.23 nm. In this dispersion system, alcalase hydrolysis expanded the protein structure, exposed hydrophobic groups and significantly improved the emulsifying activity, foaming capacity and other interface properties. The scavenging activity of DPPH free radicals and ABTS free radicals were greatly promoted, reached 59.66% and 82.91% respectively. This study provides a new idea for enzymatic hydrolysis reaction medium of zein and is conducive to the application of zein in future.

A promising self-nanoemulsifying adjuvant with plant-derived saponin D boosts immune response and exerts an anti-tumor effect.

The low immunogenicity of tumor antigens and unacceptable toxicity of adjuvants has hindered the application and development of tumor vaccines. Hence, we designed a novel anti-tumor vaccine composed of a plant-derived immunostimulant molecular nanoadjuvant (a self-nanoemulsifying system, SND) and the antigen OVA, to reinvigorate the immune response and inhibit tumor progression. In this study, this novel nanoadjuvant with Saponin D (SND) was designed and prepared by low-energy emulsification methods. Several important characteristics of the SND, including morphology, size, polymer dispersity index (PDI), zeta potential, and stability, were estimated, and the cytotoxicity of the SND was evaluated by MTT assay. Additionally, the immune response in terms of antibody titer levels and cellular immunity were evaluated in vivo after immunization with the vaccine, and the preventative and therapeutic effects of this novel vaccine against tumors were estimated. Finally, the antigen release profile was determined by IVIS imaging and by in vivo assay. This SND nanoadjuvant had good characteristics including the average particle size of 26.35 ± 0.225 nm, narrow distribution of 0.221 ± 1.76, and stability zeta potential of -12.9 ± 0.83 mV. And also, it had good stability (size, PDI, zeta potential, antigen stability) and low toxicity in vitro and in vivo, and delayed antigen release in vivo. The humoral immune response (IgG, IgG1, IgG2a, and IgG2b) and cellular immune level (cytokines of splenocytes including IFN-γ, IL-4, IL-1β andIL-17A) were both improved greatly after injected immunization at 0, 14, 28 days with the novel nanoadjuvant and antigen OVA. Importantly, this novel nanoadjuvant combined with OVA might lead to the induction of the prevent and treatment efficacy in the E.G7-OVA tumor-bearing mice. These results suggested that this novel nanoadjuvant encapsulated natural plant immunostimulant molecular OPD could be a good candidate of tumor vaccine adjuvant for reinvigorating the immune response and powerfully inhibiting tumor growth effect.