The present study investigated the anti-inflammatory and analgesic activities of novel aspirin oil-in-water (O/W) nanoemulsion and water-in-oil-in-water (W/O/W) nano multiple emulsion formulations generated using ultrasound cavitation techniques. The anti-inflammatory activities of nanoemulsion and nano multiple emulsion were determined using the λ-carrageenan-induced paw edema model. The analgesic activities of both nanoformulations were determined using acetic acid-induced writhing response and hot plate assay. For comparison, the effect of pretreatment with blank nanoemulsion and reference aspirin suspension were also studied for their anti-inflammatory and antinociceptive activities. The results showed that oral administration of nanoemulsion and nano multiple emulsion containing aspirin (60 mg/kg) significantly reduced paw edema induced by λ-carrageenan injection. Both nanoformulations decreased the number of abdominal constriction in acetic acid-induced writhing model. Pretreatment with nanoformulations led to a significant increase in reaction time in hot plate assay. Nanoemulsion demonstrated an enhanced anti-inflammatory and analgesic effects compared to reference suspension while nano multiple emulsion exhibited a mild inhibitory effects in the three experimental animal model tests. The results obtained for nano multiple emulsion were relatively lower than reference. However, administration of blank nanoemulsion did not alter the nociceptive response significantly though it showed slight anti-inflammatory effect. These experimental studies suggest that nanoemulsion and nano multiple emulsion produced a pronounced anti-inflammatory and analgesic effects in rats and may be candidates as new nanocarriers for pharmacological NSAIDs in the treatment of inflammatory disorders and alleviating pains.
To investigate the antifungal activity of conventional chitosan and chitosan-loaded nanoemulsions against anthracnose caused by Colletotrichum spp. isolated from different tropical fruits.
During recent years, there has been growing interest in the use of nanoemulsion as a drug-carrier system for topical delivery. A nanoemulsion is a transparent mixture of oil, surfactant and water with a very low viscosity, usually the product of its high water content. The present study investigated the modification of nanoemulsions with different hydrocolloid gums, to enhanced drug delivery of ibuprofen. The in vitro characterization of the initial and modified nanoemulsions was also studied.
Oil-in-water (O/W) nanoemulsions play an important key role in transporting bioactive compounds into a range of cosmeceutical products to the skin. Small droplet sizes have an inherent stability against creaming, sedimentation, flocculation, and coalescence. O/W emulsions varying in manufacturing process were prepared. The preparation and characterization of O/W nanoemulsions with average diameters of as low as 62.99 nm from palm oil esters were carried out. This was achieved using rotor-stator homogenizer and ultrasonic cavitation. Ultrasonic cell was utilized for the emulsification of palm oil esters and water in the presence of mixed surfactants, Tween 80 and Span 80 emulsions with a mean droplet size of 62.99 nm and zeta potential value at -37.8 mV. Results were comparable with emulsions prepared with rotor-stator homogenizer operated at 6000 rpm for 5 min. The stability of the emulsions was evaluated through rheology measurement properties. This included non-Newtonian viscosity, elastic modulus G', and loss modulus G″. A highly stable emulsion was prepared using ultrasonic cavitation comprising a very small particle size with higher zeta potential value and G' > G″ demonstrating gel-like behavior.
Response surface methodology (RSM) was utilized to investigate the influence of the main emulsion composition; mixture of palm and medium-chain triglyceride (MCT) oil (6%-12% w/w), lecithin (1%-3% w/w), and Cremophor EL (0.5%-1.5% w/w) as well as the preparation method; addition rate (2-20 mL/min), on the physicochemical properties of palm-based nanoemulsions. The response variables were the three main emulsion properties; particle size, zeta potential and polydispersity index. Optimization of the four independent variables was carried out to obtain an optimum level palm-based nanoemulsion with desirable characteristics. The response surface analysis showed that the variation in the three responses could be depicted as a quadratic function of the main composition of the emulsion and the preparation method. The experimental data could be fitted sufficiently well into a second-order polynomial model. The optimized formulation was stable for six months at 4 °C.
This study was conducted to develop an edible coating containing combined hydrophilic (chitosan) and hydrophobic (palm stearin) components which demonstrated gas barrier and moisture barrier properties, respectively, to prolong the post harvest life of star fruits (Averrhoa carambola L.). The emulsions of chitosan (C) and palm stearin (S) were prepared by using different ratios of C:S which were 1:0, 1:1, 1;2, 1:3, 2:1, 3:1 and 0:1. Viscosity of emulsions was studied. The physicochemical properties of coated star fruits were also evaluated in terms of weight loss, firmness, visual appearance, oxygen concentration, carbon dioxide concentration and ethylene concentration during storage at room temperature (26-28˚C) for 18 days. The results obtained showed that coating reduced weight loss, maintained firmness and appearance, slowed down the production of respiratory gases and reduced ethylene production. The most recommended coating for star fruits was C:S of 1:1 ratio as it showed good water barrier and gas barrier properties and could extend the post harvest life of star fruits up to 20 days as compared to the control samples which had a post harvest life of 12 days.
Surimi refers to concentrated myofibrial protein extracted from fish flesh by washing process. Surimi powder, is normally prepared in a dried form, and potentially useful as a raw material for preparation of seafood products. Surimi powder offers many advantages in industrial application, such as easy handling, low distribution cost, and physically convenient for addition to dry mixtures. In order to prevent the denaturation of the protein during drying, dryoprotectants such as sucrose and polyols can be added. Surimi powder is classified as fish protein concentrate type A because its protein content is higher than 65%. Surimi powder has good functional properties, such as gelation, water holding capacity, and emulsifying and foaming properties. Gel-based fish products and fish snacks are common products that can be made from surimi powder.
Covalently cross-linked nanogels were prepared via irradiation of inverse micelles that had been preparedfrom radiation crosslinkable polymer, water, oil and surfactant. A mixture of polymer, water, heptane andsodium dioctyl sulfosuccinate (AOT) at certain compositions forms inverse micelles with the size rangingfrom 2 to 8 nm. The hydrophilic head of the surfactant facilitates encapsulation of water soluble polymer.If the entrapped polymer is radiation crosslinkable, it is expected that upon irradiation, polymerizationshall take place in such small and confined space, leading to formation of nano-sized polymeric gel.Meanwhile, emulsion at 2 nm size was chosen for gamma irradiation process. The formation of thenano-sized discreet gel using irradiation of inverse micelles technique was proven at a dose as low as 5kGy to obtain nanogel sized ~ 95 nm.
The effect of degree of hydrolysis (DH) on the physicochemical properties of cobia frame hydrolysate was determined. Three levels of degree of hydrolysis of cobia frame hydrolysate were studied, which were 53%, 71% and 96%. After enzymatic hydrolysis using Alcalase®, the samples were spray-dried. Cobia hydrolysate powder samples were analyzed for their proximate analysis and physicochemical properties. The proximate analysis showed significant differences in fat and ash content only. DH96 hydrolysate showed desirable essential amino acid profile for human requirement except for methionine and isoleucine. The study found that cobia frame hydrolysate had good colour, emulsifying capacity and excellent foaming properties. However, there were no significant differences in water-holding capacity, oil-holding capacity and peptide solubility among the hydrolysate samples. This study suggested that cobia frame hydrolysate is a potential ingredient and foaming agent for food industry.
In the present investigation, the operating efficiency of a bench-top air-driven microfluidizer has been compared to that of a bench-top high power ultrasound horn in the production of pharmaceutical grade nanoemulsions using aspirin as a model drug. The influence of important process variables as well as the pre-homogenization and drug loading on the resultant mean droplet diameter and size distribution of emulsion droplets was studied in an oil-in-water nanoemulsion incorporated with a model drug aspirin. Results obtained show that both the emulsification methods were capable of producing very fine nanoemulsions containing aspirin with the minimum droplet size ranging from 150 to 170 nm. In case of using the microfluidizer, it has been observed that the size of the emulsion droplets obtained was almost independent of the applied microfluidization pressure (200-600 bar) and the number of passes (up to 10 passes) while the pre-homogenization and drug loading had a marginal effect in increasing the droplet size. Whereas, in the case of ultrasound emulsification, the droplet size was generally decreased with an increase in sonication amplitude (50-70%) and period of sonication but the resultant emulsion was found to be dependent on the pre-homogenization and drug loading. The STEM microscopic observations illustrated that the optimized formulations obtained using ultrasound cavitation technique are comparable to microfluidized emulsions. These comparative results demonstrated that ultrasound cavitation is a relatively energy-efficient yet promising method of pharmaceutical nanoemulsions as compared to microfluidizer although the means used to generate the nanoemulsions are different.
Micro-emulsions and sometimes nano-emulsions are well known candidates to deliver drugs locally. However, the poor rheological properties are marginally affecting their acceptance pharmaceutically. This work aimed to modify the poor flow properties of a nano-scaled emulsion comprising palm olein esters as the oil phase and ibuprofen as the active ingredient for topical delivery. Three Carbopol ® resins: 934, 940 and Ultrez 10, were utilized in various concentrations to achieve these goals. Moreover, phosphate buffer and triethanolamine solutions pH 7.4 were used as neutralizing agents to assess their effects on the gel-forming and swelling properties of Carbopol ® 940. The addition of these polymers caused the produced nano-scaled emulsion to show a dramatic droplets enlargement of the dispersed globules, increased intrinsic viscosity, consistent zeta potential and transparent-to-opaque change in appearance. These changes were relatively influenced by the type and the concentration of the resin used. Carbopol ® 940 and triethanolamine appeared to be superior in achieving the proposed tasks compared to other materials. The higher the pH of triethanolamine solution, the stronger the flow-modifying properties of Carbopol ® 940. Transmission electron microscopy confirmed the formation of a well-arranged gel network of Carbopol ® 940, which was the major cause for all realized changes. Later in vitro permeation studies showed a significant decrease in the drug penetration, thus further modification using 10% w/w menthol or limonene as permeation promoters was performed. This resulted in in vitro and in vivo pharmacodynamics properties that are comparably higher than the reference chosen for this study.
A novel microgels were polymerized using styrene (St), methyl methacrylate (MMA), acrylamide (AAm), and acrylic acid (AAc) monomers in the presence of N,N'-methylenebisacrylamide (MBA) cross-linker. Pre-emulsified monomer was first prepared followed by polymerizing monomers using semi-batch emulsion polymerization. Fourier Transform Infrared Spectroscopy (FTIR) and (1)H Nuclear Magnetic Resonance (NMR) were used to determine the chemical structure and to indentify the related functional group. Grafting and cross-linking of poly(acrylamide-co-acrilic acid)-grafted-poly(styrene-co-methyl methacrylate) [poly(AAm-co-AAc)-g-poly(St-co-MMA)] microgels are approved by the disappearance of band at 1300 cm(-1), 1200 cm(-1) and 1163 cm(-1) of FTIR spectrum and the appearance of CH peaks at 5.5-5.7 ppm in (1)H NMR spectrum. Scanning Electron Microscope (SEM) images indicated that poly(St-co-MMA) particle was lobed morphology coated by cross-linked poly(AAm-co-AAc) shell. Furthermore, SEM results revealed that poly(AAm-co-AAc)-g-poly(St-co-MMA) is composite particle that consist of "raspberry"-shape like structure core. Internal structures of the microgels showed homogeneous network of pores, an extensive interconnection among pores, thicker pore walls, and open network structures. Water absorbency test indicated that the sample with particle size 0.43 μm had lower equilibrium water content, % than the sample with particle size 7.39 μm.
The present investigation focuses in investigating the effect of osmotic pressure, gelling on the mean droplet diameter, polydispersity index, droplet size stability of the developed novel Aspirin containing water-in-oil-in-water (W/O/W) nano multiple emulsion. The aspirin-loaded nano multiple emulsion formulation was successfully generated using two-stage ultrasonic cavitational emulsification which had been reported in author's previous study. The osmotic behavior of ultrasonically prepared nano multiple emulsions were also examined with different glucose concentrations both in the inner and outer aqueous phases. In addition, introducing gelatin into the formulation also observed to play an important role in preventing the interdroplet coalescence via the formation of interfacial rigid film. Detailed studies were also made on the possible mechanisms of water migration under osmotic gradient which primarily caused by the permeation of glucose. Besides, the experimental results have shown that the interfacial tension between the two immiscible phases decreases with varying the composition of organic phase. Although the W/O/W emulsion prepared with the inner/outer glucose weight ratio of 1-0.5% (w/w) showed an excellent droplet stability, the formulation containing 0.5% (w/w) glucose in the inner aqueous phase appeared to be the most stable with minimum change in the mean droplet size upon one-week storage period. Based on the optimization, nano multiple emulsion droplets with the mean droplet diameter of around 400 nm were produced using 1.25% (w/w) Span 80 and 0.5% Cremophore EL. Overall, our investigation makes a pathway in proving that the use of ultrasound cavitation is an efficient yet promising approach in the generation of stable and uniform nano multiple emulsions and could be used in the encapsulation of various active pharmaceutical ingredients in the near future.
The main objective of the current work was to characterize the shear rheological flow behaviour and emulsifying properties of the natural biopolymer from durian seed. The present study revealed that the extraction condition significantly affected the physical and functional characteristics of the natural biopolymer from durian seed. The dynamic oscillatory test indicated that the biopolymer from durian seed showed more gel (or solid) like behaviour than the viscous (or liquid) like behaviour (G'>G″) at a relatively high concentration (20%) in the fixed frequency (0.1 Hz). This might be explained by the fact that the gum coils disentangle at low frequencies during the long period of oscillation, thus resulting in more gel like behaviour than the viscous like behaviour. The average droplet size of oil in water (O/W) emulsions stabilized by durian seed gum significantly varied from 0.42 to 7.48 μm. The results indicated that O/W emulsions showed significant different stability after 4 months storage. This might be interpreted by the considerable effect of the extraction condition on the chemical and molecular structure of the biopolymer, thus affecting its emulsifying capacity. The biopolymer extracted by using low water to seed (W/S) ratio at the low temperature under the alkaline condition showed a relatively high emulsifying activity in O/W emulsion.
Fatty acid esters are long-chain esters, produced from the reaction of fatty acids and alcohols. They possess potential applications in cosmetic and pharmaceutical formulations due to their excellent wetting behaviour at interfaces and a non-greasy feeling when applied on the skin surfaces. This preliminary work was carried out to construct pseudo-ternary phase diagrams for oleyl laurate, oleyl stearate and oleyl oleate with surfactants and piroxicam. Then, the preparation and optimization study via 'One-At-A-Time Approach' were carried out to determine the optimum amount of oil, surfactants and stabilizer using low-energy emulsification method. The results revealed that multi-phase region dominated the three pseudo-ternary phase diagrams. A composition was chosen from each multi-phase region for preparing the nanoemulsions systems containing piroxicam by incorporating a hydrocolloid stabilizer. The results showed that the optimum amount (w/w) of oil for oleyl laurate nanoemulsions was 30 and 20 g (w/w) for oleyl stearate nanoemulsions and oleyl oleate nanoemulsions. For each nanoemulsions system, the amount of mixed surfactants and stabilizer needed for the emulsification to take place was found to be 10 and 0.5 g (w/w), respectively. The emulsification process via high-energy emulsification method successfully produced nano-sized range particles. The nanoemulsions systems passed the centrifugation test and freeze-thaw cycle with no phase failures, and stable for 3 months at various storage temperatures (3°C, 25°C and 45°C). The results proved that the prepared nanoemulsions system cannot be formed spontaneously, and thus, energy input was required to produce nano-sized range particles.
Toxicological studies constitute an essential part of the effort in developing an herbal medicine into a drug product. A newly developed thymoquinone-rich fraction nanoemulsion (TQRFNE) has been prepared using a high pressure homogenizer. The purpose of this study was to investigate the potential acute toxicity of this nanoemulsion in Sprague Dawley rats. The acute toxicity studies were conducted as per the OECD guidelines 425, allowing for the use of test dose limit of 20 mL TQRFNE (containing 44.5 mg TQ)/kg. TQRFNE and distilled water (DW) as a control were administered orally to both sexes of rats on Day 0 and observed for 14 days. All the animals appeared normal, and healthy throughout the study. There was no observed mortality or any signs of toxicity during the experimental period. The effects of the TQRFNE and DW groups on general behavior, body weight, food and water consumption, relative organ weight, hematology, histopathology, and clinical biochemistry were measured. All the parameters measured were unaffected as compared to the control (DW) group. The administration of 20 mL TQRFNE /kg was not toxic after an acute exposure.
Self-assembled nanocarriers attract increasing attention due to their wide application in various practical fields; among them, one of the most focused fields is drug delivery. Appropriate selection of surfactant is the basis for preparing a successful nanocarrier. Until now, from phospholipid to synthetic surfactants, many surfactants have been used to explore a suitable drug delivery vehicle for the complex in-vivo environment. Among all, bio surfactants are found to be more suitable due to their bio-origin, less-toxicity, biodegradability, cheaper rate and above all, their versatile molecular structures. This molecular property enables them to self assemble into fascinating structures. Moreover, binding DNA, enhancing pH sensitivity and stability allows novelty over their synthetic counterparts and phospholipid. This review paper focuses on the properties and applications of bio-nano-carriers for drug delivery. Micelle, microemulsion, and vesicle are the three nanocarriers which are discussed herein.
The bioaccessibility of eicosapentaenoic acid (EPA) in the forms of monoacylglycerol (EPA-MAG), triacylglycerol (EPA-TAG), and phospholipid (EPA-PL) during gastrointestinal passage was compared in this study using a dynamic gastrointestinal model (TIM system). The TIM system simulated the average upper gastrointestinal tract conditions of healthy human adults after intake of a meal (fed state conditions). In this study, the three EPA-rich oils were separately homogenized with full fat milk to obtain oil-in-water emulsions. Plain yogurt was added into the mixture at an emulsion/yogurt ratio of 4:1 (w/w) as the food matrix of the test products. The results show that the test meals containing EPA-PL left the stomach compartment most efficiently in comparison with the gastric emptying of EPA-MAG and EPA-TAG. The PLs also showed a significantly (P < 0.05) higher bioaccessibility of EPA (75-80%) in comparison with MAG (30%) and TAG (38%). The better gastric emptying of EPA-PL was likely related to the more stable emulsion of EPA-PL in the test meal. EPA-PL was delivered within the meal matrix into the duodenum instead of floating on the top of the test meal matrix. EPA-MAG had the highest amount of EPA that did not leave the stomach (68% of the test meal). The results from this work indicate that EPA-PL is a more effective form of EPA for a higher lipid bioaccessibility than MAG and TAG under the test conditions.
Palm kernel oil esters nanoemulsion-loaded with chloramphenicol was optimized using response surface methodology (RSM), a multivariate statistical technique. Effect of independent variables (oil amount, lecithin amount and glycerol amount) toward response variables (particle size, polydispersity index, zeta potential and osmolality) were studied using central composite design (CCD). RSM analysis showed that the experimental data could be fitted into a second-order polynomial model. Chloramphenicol-loaded nanoemulsion was formulated by using high pressure homogenizer. The optimized chloramphenicol-loaded nanoemulsion response values for particle size, PDI, zeta potential and osmolality were 95.33nm, 0.238, -36.91mV, and 200mOsm/kg, respectively. The actual values of the formulated nanoemulsion were in good agreement with the predicted values obtained from RSM. The results showed that the optimized compositions have the potential to be used as a parenteral emulsion to cross blood-brain barrier (BBB) for meningitis treatment.
This paper deals with the conjugation of durian seed gum (DSG) with whey protein isolate (WPI) through Maillard reactions. Subsequently, the functional properties of durian seed gum in the non-conjugated (control sample) and conjugated forms were compared with several commercial gums (i.e., Arabic gum, sodium alginate, kappa carrageenan, guar gum, and pectin). The current study revealed that the conjugation of durian seed gum with whey protein isolate significantly (p < 0.05) improved its foaming properties. In this study, the conjugated durian seed gum produced the most stable foam among all samples. On the other hand, the emulsion stabilized with the conjugated durian seed gum also showed more uniform particles with a larger specific surface area than the emulsion containing the non-conjugated durian seed gum. The conjugated durian seed gum showed significant different foaming properties, specific surface area, particle uniformity and water holding capacity (WHC) as compared to the target polysaccharide gums. The conjugated durian seed gum showed more similar functional properties to Arabic gum rather than other studied gums.