Neuromuscular Polytrauma Pain is Resolved by Macrophage COX-2 Nanoimmunomodulation.

Soft tissue injuries often involve muscle and peripheral nerves and are qualitatively distinct from single-tissue injuries. Prior research suggests that damaged innervation compromises wound healing. To test this in a traumatic injury context, we developed a novel mouse model of nerve and lower limb polytrauma, which features greater pain hypersensitivity and more sustained macrophage infiltration than either injury in isolation. We also show that macrophages are crucial mediators of pain hypersensitivity in this model by delivering macrophage-targeted nanoemulsions laden with the cyclooxygenase-2 (COX-2) inhibitor celecoxib. This treatment was more effective in males than females, and more effective when delivered 3 days post-injury than 7 days post-injury. The COX-2 inhibiting nanoemulsion drove widespread anti-inflammatory changes in cytokine expression in polytrauma-affected peripheral nerves. Our data shed new light on the modulation of inflammation by injured nerve input and demonstrate macrophage-targeted nanoimmunomodulation can produce rapid and sustained pain relief following complex injuries.

Influences of ultrasonic treatment on the physicochemical properties and microstructure of diacylglycerol-loaded emulsion stabilized with soybean protein isolate and sodium alginate.

This study examined the impacts of ultrasonic power (0, 150, 300, 450, 600, and 750 W) and ultrasonic durations (3, 6, 9, 12, and 15 min) on the physicochemical properties and microstructure of diacylglycerol (DAG)-loaded emulsions stabilized with soybean protein isolate (SPI) and sodium alginate (SA). The findings indicated that the smallest particle size, zeta potential, and contact angle for SPI-SA-DAG emulsions were respectively 5.58 µm, -49.85 mV, and 48.65°, achieved at an ultrasonic power of 450 W. The emulsification properties, loss modulus, storage modulus, and apparent viscosity of the emulsions were optimal at this power setting and at a duration of 9 min. Analytical techniques, including confocal laser scanning-, scanning electron-, and atomic force microscopy, revealed that ultrasonication significantly altered emulsion aggregation state, with the surface roughness (Rq) being minimized at 450 W. These results demonstrated that the stability of SPI-SA-DAG emulsions can be effectively enhanced by an appropriate ultrasonic treatment at 450 W for 9 min. This research provides theoretical support for the broad application of sonication techniques in the food industry.

Surface-Charge Tuned Polymeric Nanoemulsions for Carvacrol Delivery in Interkingdom Biofilms.

Biofilms, intricate microbial communities entrenched in extracellular polymeric substance (EPS) matrices, pose formidable challenges in infectious disease treatment, especially in the context of interkingdom biofilms prevalent in the oral environment. This study investigates the potential of carvacrol-loaded biodegradable nanoemulsions (NEs) with systematically varied surface charges─cationic guanidinium (GMT-NE) and anionic carboxylate (CMT-NE). Zeta potentials of +25 mV (GMT-NE) and -33 mV (CMT-NE) underscore successful nanoemulsion fabrication (∼250 nm). Fluorescent labeling and dynamic tracking across three dimensions expose GMT-NE's superior diffusion into oral biofilms, yielding a robust antimicrobial effect with 99.99% killing for both streptococcal and Candida species and marked reductions in bacterial cell viability compared to CMT-NE (∼4-log reduction). Oral mucosa tissue cultures affirm the biocompatibility of both NEs with no morphological or structural changes, showcasing their potential for combating intractable biofilm infections in oral environment. This study advances our understanding of NE surface charges and their interactions within interkingdom biofilms, providing insights crucial for addressing complex infections involving bacteria and fungi in the demanding oral context.

Intact NMR Approach Quickly Reveals Synchronized Microstructural Changes in Oil-in-Water Nanoemulsion Formulations.

A soft-core oil-in-water (o/w) nanoemulsion (NE) is composed of nanometer (nm) sized oil droplets, stabilized by a surfactant layer and dispersed in a continuous bulky water phase. Characterization of the o/w NE molecule arrangements non-invasively, particularly the drug phase distribution (DPD) and its correlation to oil globule size (OGS), remains a challenge. Here we demonstrated the analytical methods of intact 19F Nuclear Magnetic Resonance (NMR) and 1H diffusion ordered spectroscopy (DOSY) NMR for their specificity in measuring DPD and OGS, respectively, on three NE formulations containing the active ingredient difluprednate (DFPN) at the same concentration. The results illustrated synchronized molecular rearrangement reflected in the DPD and OGS upon alterations in formulation. Addition of surfactant resulted in a higher DPD in the surfactant layer, and concomitantly smaller OGS. Mechanic perturbation converted most of the NE globules to the smaller thermodynamically stable microemulsion (ME) globules, changing both DPD and OGS to ME phase. These microstructure changes were not observed using 1D 1H NMR; and dynamic light scattering (DLS) was only sensitive to OGS of ME globule in mechanically perturbed formulation. Collectively, the study illustrated the specificity and essential role of intact NMR methods in measuring the critical microstructure attributes of soft-core NE systems quickly, accurately, and non-invasively. Therefore, the selected NMR approach can be a unique diagnostic tool of molecular microstructure or Q3 property in o/w NE formulation development, and quality assurance after manufacture process or excipient component changes.

Lipid Emulsions Inhibit Labetalol-Induced Vasodilation in the Isolated Rat Aorta.

Lipid emulsions are used as adjuvant drugs to alleviate intractable cardiovascular collapse induced by drug toxicity. We aimed to examine the effect of lipid emulsions on labetalol-induced vasodilation and the underlying mechanism in the isolated rat aorta. We studied the effects of endothelial denudation, NW-nitro-l-arginine methyl ester (l-NAME), calmidazolium, methylene blue, 1H-[1,2,4]oxadiazolo[4,3-a] quinoxalin-1-one (ODQ), and lipid emulsions on labetalol-induced vasodilation. We also evaluated the effects of lipid emulsions on cyclic guanosine monophosphate (cGMP) formation, endothelial nitric oxide synthase (eNOS) phosphorylation, and endothelial calcium levels induced by labetalol. Labetalol-induced vasodilation was higher in endothelium-intact aortas than that in endothelium-denuded aortas. l-NAME, calmidazolium, methylene blue, and ODQ inhibited labetalol-induced vasodilation in endothelium-intact aortas. Lipid emulsions inhibited labetalol-induced vasodilation in endothelium-intact and endothelium-denuded aortas. l-NAME, ODQ, and lipid emulsions inhibited labetalol-induced cGMP formation in endothelium-intact aortas. Lipid emulsions reversed the stimulatory and inhibitory eNOS (Ser1177 and Thr495) phosphorylation induced by labetalol in human umbilical vein endothelial cells and inhibited the labetalol-induced endothelial calcium increase. Moreover, it decreased labetalol concentration. These results suggest that lipid emulsions inhibit vasodilation induced by toxic doses of labetalol, which is mediated by the inhibition of endothelial nitric oxide release and reduction of labetalol concentration.

Alternatives to Conventional Topical Dosage Forms for Targeted Skin Penetration of Diclofenac Sodium.

Skin penetration of an active pharmaceutical ingredient is key to developing topical drugs. This penetration can be adjusted for greater efficacy and/or safety through the selection of dosage form. Two emerging dosage forms, cream-gel and gel-in-oil emulsion, were tested for their ability to deliver diclofenac into the skin, with the target of maximising skin retention while limiting systemic exposure. Prototypes with varying amounts of solvents and emollients were formulated and evaluated by in vitro penetration testing on human skin. Cream-gel formulas showed better skin penetration than the emulgel benchmark drug even without added solvent, while gel-in-oil emulsions resulted in reduced diffusion of the active into the receptor fluid. Adding propylene glycol and diethylene glycol monoethyl ether as penetration enhancers resulted in different diclofenac penetration profiles depending on the dosage form and whether they were added to the disperse or continuous phase. Rheological characterisation of the prototypes revealed similar profiles of cream-gel and emulgel benchmark, whereas gel-in-oil emulsion demonstrated flow characteristics suitable for massaging product into the skin. This study underlined the potential of cream-gel and gel-in-oil emulsions for adjusting active penetration into the skin, broadening the range of choices available to topical formulation scientists.

Suspensions of antibiotics in self-emulsifying oils as a novel approach to formulate eye drops with substances which undergo hydrolysis in aqueous environment.

The aim of this study was to develop eye-drops with cefuroxime (CEF) sodium or vancomycin (VAN) hydrochloride, antibiotics that are instable in water. Anhydrous self-emulsifying oils (SEO) are proposed as a carrier and antibiotics are suspended. In the contact with tear fluid, the formulation should transform into emulsion, with fast dissolution of an antibiotic. CEF or VAN (5% w/w) was suspended in SEO carriers prepared by dissolving surfactants (Tween 20 or Span 80 5% w/w) in Miglyol, castor oil, or olive oil. Formulations with or without sodium citrate (2% w/w) were compared. Six-months or 1-year stability tests were carried out at 40 °C. The content of CEF and VAN was evaluated using HPLC and the potency of the antibiotic was assessed with agar diffusion method. In contact with water, drug particles suspended in SEO dissolved rapidly and o/w emulsion was formed. After 1-year at 40 °C, the content of degradation products was at most 0.5% in CEF and 4.0% in VAN formulations. The agar diffusion assay has shown that CEF and VAN loaded into SEO retained its potency against the sensitive microorganisms comparable to an aqueous solution. Therefore, SEO can be used as a novel carrier for the active substances which may not require improved solubility or absorption but need to be protected from moisture. This is a formulation that can be produced on industrial scale, with no limitation of stability or drug concentration.

Intravenous lipid emulsion interference in coagulation testing: an ex vivo analysis.

INTRODUCTION: Intravenous lipid emulsion is used in the rescue treatment of certain poisonings. A complication is interference with laboratory analyses. The aim of this study was to determine the impact of intravenous lipid emulsion on routine laboratory analysis of coagulation parameters ex vivo and determine if any of the analytical techniques remain reliable. METHODS: Samples were obtained from 19 healthy volunteers and divided in triplicate. One sample served as a control, and the other two were diluted to simulate the treatment of an average adult with Intralipid® 20 per cent Fresenius Kabi 100 mL (dilution-1) or 500 mL (dilution-2). Coagulation tests performed were prothrombin time, activated prothrombin time, D-dimer concentration and fibrinogen. Coagulation testing was performed by three techniques. Test-1 was performed on a Sysmex CN6000 analyzer. Test-2 was performed with a manual mechanical endpoint method using the semi-automated Stago KC4 Delta. Test-3 involved high-speed centrifugation before repeat testing on the Sysmex CN6000 analyzer. RESULTS: For test-1, only nine (47 per cent) samples in dilution-1 could be analyzed for coagulation tests, and no coagulation tests could be analyzed for dilution-2 because of lipaemia. For test-2 and test-3, all samples could be analyzed, and all results of both testing methods fell within the limits of the laboratory reference range. DISCUSSION: Difficulties in laboratory analysis of patients having received intravenous lipid emulsion are due to multiple factors. Most automated coagulation analyzers use optical measurements, which can be unreliable in the presence of a high intravenous lipid concentration. By altering the lipaemia in the testing solution using high-speed centrifugation or by using manual mechanical endpoint detection, we were able to obtain reliable results. These findings are limited by the use of an ex vivo method and healthy volunteers. CONCLUSIONS: This ex vivo model confirms that Intralipid® interferes with routine coagulation studies. It is important that clinicians are aware and inform their laboratories of its administration.

Investigating the effects of oil type, emulsifier type, and emulsion particle size on textured fibril soy protein emulsion-filled gels and soybean protein isolate emulsion-filled gels.

The effects of oil type, emulsifier type, and emulsion particle size on the texture, gel strength, and rheological properties of SPI emulsion-filled gel (SPI-FG) and TFSP emulsion-filled gel (TFSP-FG) were investigated. Using soybean protein isolate or sodium caseinate as emulsifiers, emulsions with cocoa butter replacer (CBR), palm oil (PO), virgin coconut oil (VCO), and canola oil (CO) as oil phases were prepared. These emulsions were filled into SPI and TFSP gel substrates to prepare emulsion-filled gels. Results that the hardness and gel strength of both gels increased with increasing emulsion content when CBR was used as the emulsion oil phase. However, when the other three liquid oils were used as the oil phase, the hardness and gel strength of TFSP-FG decreased with the increasing of emulsion content, but those of SPI-FG increased when SPI was used as emulsifier. Additionally, the hardness and gel strength of both TFSP-FG and SPI-FG increased with the decreasing of mean particle size of emulsions. Rheological measurements were consistent with textural measurements and found that compared with SC, TFSP-FG, and SPI-FG showed higher G' values when SPI was used as emulsifier. Confocal laser scanning microscopy (CLSM) observation showed that the distribution and stability of emulsion droplets in TFSP-FG and SPI-FG were influenced by the oil type, emulsifier type and emulsion particle size. SPI-stabilized emulsion behaved as active fillers in SPI-FG reinforcing the gel matrix; however, the gel matrix of TFSP-FG still had many void pores when SPI-stabilized emulsion was involved. In conclusion, compared to SPI-FG, the emulsion filler effect that could reinforce gel networks became weaker in TFSP-FG.

Preparation of Microsponge Drug Delivery System (MSDDS) Followed by a Scale-Up Approach.

In 1987, Won invented the solid-phase porous microsphere (MS), which stores bioactive compounds in many interconnected voids. Spherical particles (5-300 µm), MS, may form clusters of smaller spheres, resulting in many benefits. The current investigation focussed on gel-encased formulation, which can be suitable for dermal usage. First, quasi-emulsion (w/o/w) solvent evaporation was used to prepare 5-fluorouracil (5 FU) MS particles. The final product was characterized (SEM shows porous structure, FTIR and DSC showed drug compatibility with excipients, and gel formulation is shear-thinning) and further scaled up using the 8-fold method. Furthermore, CCD (Central Composite Design) was implemented to obtain the optimized results. After optimizing the conditions, including the polymer (600 mg, ethyl cellulose (EC), eudragit RS 100 (ERS)), stirring speed (1197 rpm), and surfactant concentration (2% w/v), we achieved the following results: optimal yield (63%), mean particle size (152 µm), drug entrapment efficiency (76%), and cumulative drug release (74.24% within 8 h). These findings are promising for industrial applications and align with the objectives outlined in UN Sustainable Development Goals 3, 9, and 17, as well as the goals of the G20 initiative.

Improving the storage quality of Harbin red sausages by quaternized chitosan/sodium alginate coating curcumin nano-emulsion.

In this study, the effect of sodium alginate and quaternized chitosan bis-polysaccharide-based shell transport curcumin nano-emulsions (Cur@QCS/SA) on the microbiological, physicochemical properties, quality characteristics of Harbin red sausage during storage is investigated. According to the microbiological results, the shelf life of Harbin red sausage is extended from 3 d to 6 d by adding 0.15% Cur@QCS/SA, and Bacillus is the most predominant bacterial before 6 d. Additionally, the physicochemical properties change significantly, the pH, weight loss (WL), water holding capacity (WHC), water activity (aw), L*, and a* of red sausage decrease gradually with the extension of storage time, as well as b*, lipid oxidation, proteolysis increase significantly (P < 0.05). Secondly, it is found that 0.15% treatment group can better maintain the quality characteristics of Harbin red sausage according to texture profile analysis (TPA), electronic nose (E-nose), and electronic tongue (E-tongue) (P < 0.05). This study provides a new way for nano-emulsions in food applications and a new option for the preservation of Harbin red sausage as well as other low-temperature meat products.

Replacing the animal fat in Bologna sausages using high internal phase emulsion stabilized with lentil protein isolate (Lens culinaris).

High internal phase emulsions (HIPEs) are promising techniques that can replace saturated fat in food without reducing the product's texture, sensory attributes, water-holding capacity, and cooking loss. In the current investigation, 100% pork back fat was replaced by HIPEs formed with lentil protein isolate (LPI) in Bologna sausages. HIPEs were prepared by 25% LPI dispersion (2, 4, 6, and 8%, w/w) and 75% (w/w) soybean oil. HIPEs with higher LPI concentration (4, 6, and 8%, w/w) showed lower droplet size, firmer appearance, and better rheology behavior than 2% LPI. The concentrations LPI (2%, 4%, 6%, and 8%, w/w) led to increased moisture in sausages (FH2, FH4, FH6, and FH8, respectively) compared to the FC. These LPI levels resulted in sausage values for pressed juice similar to the FC and lower energy values than sausages with soybean oil (FO) and pork back fat (FC). Besides, these LPI concentrations (4%, 6%, and 8%, w/w) resulted in a lower oil oxidation level in sausages with HIPEs (FH4, FH6, and FH8, respectively) compared to the control sausage formulation with pork back fat (FC). Bologna sausages elaborated with HIPEs showed emulsion stability values higher than 97%, without significance difference between them. The texture and sensory properties of sausages made with HIPEs were comparable to those made with pork back fat. HIPEs may improve the oxidation stability of the Bologna sausages. These results highlight the effectiveness of HIPEs structured with lentil protein in successfully substituting pork back fat in Bologna sausages with a better nutritional appeal.

Modification of casein with oligosaccharides via the Maillard reaction: As natural emulsifiers.

In the present study, different oligosaccharides (fructooligosaccharide (FOS), galactooligosaccharide (GOS), isomaltooligosaccharide (IMO), and xylooligosaccharide (XOS)) were modified on casein (CN) via Maillard reaction. The CN-oligosaccharide conjugates were evaluated for modifications to functional groups, fluorescence intensity, water- and oil-holding properties, emulsion foaming properties, as well as general emulsion properties and stability. The results demonstrated that the covalent combination of CN and oligosaccharides augmented the spatial repulsion and altered the hydrophobic milieu of proteins, which resulted in a diminution in water-holding capacity, an augmentation in oil-holding capacity, and an enhancement in the emulsification properties of proteins. Among them, CN-XOS exhibited the most pronounced changes, with the emulsification activity index and emulsion stability index increasing by approximately 72% and 84.3%, respectively. Furthermore, CN-XOS emulsions have smaller droplet sizes and higher absolute potential values than CN emulsions. Additionally, CN-XOS emulsions demonstrate remarkable stability when ion concentration and pH are varied. These findings indicate that oligosaccharides modified via Maillard reaction can be used as good natural emulsifiers. This provides a theoretical basis for using oligosaccharides to modify proteins and act as natural emulsifiers.

Advances of protein-based emulsion gels as fat analogues: Systematic classification, formation mechanism, and food application.

Fat plays a pivotal role in the appearance, flavor, texture, and palatability of food. However, excessive fat consumption poses a significant risk for chronic ailments such as obesity, hypercholesterolemia, and cardiovascular disease. Therefore, the development of green, healthy, and stable protein-based emulsion gel as an alternative to traditional fats represents a novel approach to designing low-fat food. This paper reviews the emulsification behavior of proteins from different sources to gain a comprehensive understanding of their potential in the development of emulsion gels with fat-analog properties. It further investigates the emulsifying potential of protein combined with diverse substances. Then, the mechanisms of protein-stabilized emulsion gels with fat-analog properties are discussed, mainly involving single proteins, proteins-polysaccharides, as well as proteins-polyphenols. Moreover, the potential applications of protein emulsion gels as fat analogues in the food industry are also encompassed. By combining natural proteins with other components such as polysaccharides, polyphenols, or biopolymers, it is possible to enhance the stability of the emulsion gels and improve its fat-analog texture properties. In addition to their advantages in protecting oil oxidation, limiting hydrogenated oil intake, and delivering bioactive substances, protein-based emulsion gels have potential in food 3D printing and the development of specialty fats for plant-based meat.

Encapsulation of lycopene in Pickering emulsion stabilized by complexes of whey protein isolate fibrils and sodium alginate: Physicochemical property, structural characterization and in vitro digestion property.

In present study, whey protein isolate fibrils and sodium alginate complexes (WPIFs-SA) were prepared and further used to stabilize Pickering emulsions for lycopene delivery. The optimal interaction between WPIFs and SA occurred at pH 3.0, with a mass ratio of 2:1. Increasing the oil fractions and the content of WPIFs-SA complexes significantly improved Pickering emulsions' stability, concurrently reducing droplet size and increasing viscoelasticity. Meanwhile, it facilitated the formation of a thicker protective layer and a compact network structure around the oil droplets, offering better protection for lycopene against thermal and photo degradation. In vitro digestion studies revealed that as the oil fractions and complex contents increased, the lipolysis degree decreased. The engineered WPIFs-SA Pickering emulsion could be used as an innovative delivery system for the protection and delivery of lycopene.

Interactive roles of co-solvents and lemon-oil composition in the fabrication of dilutable clear emulsions.

Clear emulsions are used as flavor carriers by the beverage industry because of their favorable optical properties. A transparent microemulsion with small droplets requires a high concentration of surfactants, and is often non-dilutable, posing a significant challenge to their application in the food industry. The formation of dilutable microemulsions by modulating the compatibility of oil composition and co-solvents was studied. While single-fold lemon oil exhibited poor loading capacity overall, no precipitation occurred due to the stronger interaction between monoterpenes and sucrose monopalmitate (SMP). Conversely, emulsification of five-fold lemon oil with 20 % ethanol demonstrated a higher loading capacity and a stronger dilution stability than other lemon oils. This is likely due to the balanced composition of surface-active monoterpenes and other components in five-fold lemon oil which facilitated the effective use of micellar space and aided in the retention of both surfactants and co-solvents post-dilution. The emulsification of higher-folded lemon oil, however, was favored by the use of propylene glycol as a surfactant exhibiting stronger dilution stability than ethanol, though it required twice as much co-solvent. The high concentration of surface-active monoterpene in the lower-folded lemon oils competes with propylene glycol for interfacial incorporation. This study demonstrated that co-solvents and oil composition play interactive roles in producing dilutable optically clear emulsions, and it provides a blueprint for the food industry to design colloidal systems using a minimum of surfactants.

Enhanced bioaccessibility of interfacial delivered oleanolic acid through self-constructed Pickering emulsion: Effects of oil types.

Pentacyclic triterpenes have attracted much attention because of their many bioactivities, but their bioaccessibility is low. Oleanolic acid (OA) was used in this study as a typical edible pentacyclic triterpene. In this work, we proposed an OA interfacial delivery model based on W/O Pickering emulsion, and investigated the effects of different oil types on the emulsion properties and OA bioaccessibility of the OA W/O Pickering emulsion interfacial delivery system (EIDS). Medium chain triglyceride (MCT), long chain triglycerides (LCT) and MCT/LCT (1:1, w/w) were selected as carrier oils for the preparation of emulsions, respectively. The results showed that the emulsions formed from LCT had smaller particle sizes, which increased the deformation resistance of the emulsions and exhibited good stability during the simulated in vitro digestion. The extent of free fatty acid (FFA) release during oil digestion was MCT (103.32 ± 3.74 %) > M/L (97.89 ± 2.89 %) > LCT (71.41 ± 6.64 %). Of interest, the bioaccessibility of OA was influenced by the carrier oil: LCT (59.34 ± 2.55 %) > M/L (47.35 ± 6.25 %) > MCT (13.11 ± 1.40 %) ＞ PBS (7.11 ± 1.74 %), and such a difference was mainly attributed to the greater solubilisation of OA in mixed micelles consisting of long-chain fatty acids. In summary, the size of hydrophobic domains in the mixed micelles produced a greater effect than the effect of FFA release on OA bioaccessibility. This study provides a theoretical basis for the interfacial delivery of OA and the enhancement of OA bioaccessibility based on W/O Pickering emulsions with different oil types.

Impact of lipid droplet characteristics on the rheology of plant protein emulsion gels: Droplet size, concentration, and interfacial properties.

Plant-based meat analogs are being developed to address environmental, sustainability, health, and animal welfare concerns associated with real meat products. However, it is challenging to mimic the desirable physicochemical, functional, and sensory properties of real meat products using plant-based ingredients. Emulsion gels consisting of lipid droplets embedded in biopolymer matrices are commonly used to create products with appearances, textures, and sensory attributes like meat products. In this study, the impact of soybean oil droplet characteristics (concentration, size, and charge) on the physicochemical properties of potato protein gels was studied. The oil droplets were either coated by a non-ionic surfactant (Tween 20) or a plant protein (patatin) to obtain different surface properties. The introduction of the oil droplets caused the protein gels to change from mauve to off-white, which was attributed to increased light scattering. Increasing the oil droplet concentration in the emulsion gels decreased their shear modulus and Young's modulus, which was mainly attributed to the fact that the oil droplets were less rigid than the surrounding protein network. Moreover, increasing the oil droplet size made this effect more pronounced, which was attributed to their greater deformability. Competitive adsorption of proteins and surfactants at the oi-water interface in the Tween emulsion promoted emulsion instability. This research highlights the complexity of the interactions between oil droplets and protein networks in emulsion gels. These insights are important for the utilization of emulsion gels in the formulation of plant-based foods with improved quality attributes.

Preparation of nanoparticle and nanoemulsion formulations containing repaglinide and determination of pharmacokinetic parameters in rats.

Repaglinide (RPG) belongs to the class of drugs known as meglitinides and is used for improving and maintaining glycemic control in the treatment of patients with Type 2 diabetes. RPG is a Class II drug (BCS) because of its high permeability and low water solubility. It also undergoes hepatic first-pass metabolism. The oral bioavailability of RPG is low (about 56 %) due to these drawbacks. Our aim in this study is to prepare two different nano-sized drug carrier systems containing RPG (nanoparticle: RPG-PLGA-Zein-NPs or nanoemulsion: RPG-NE) and to carry out a pharmacokinetic study for these formulations. We prepared NPs using PLGA and Zein. In addition, a single NE formulation was developed using Tween 80 and Pluronic F68 as surfactants and Labrasol as co-surfactant. The droplet size values of the blank-NE and RPG-NE formulations were found to be less than 120 nm. The mean particle sizes of blank-Zein-PLGA-NPs and RPG-Zein-PLGA-NPs were less than 260 nm. The Cmax and tmax values of RPG-Zein-PLGA-NPs and RPG-NE (523 ± 65 ng/mL and 770 ± 91 ng/mL; 1.41 ± 0.46 h and 1.61 ± 0.37 h, respectively) were meaningfully higher than those of free RPG (280 ± 33 ng/mL; 0.72 ± 0.28 h) (p < 0.05). The AUC0-∞ values calculated for RPG-Zein-PLGA-NPs and RPG-NE were approximately 4.04 and 5.05 times higher than that calculated for free RPG. These nanosized drug delivery systems were useful in increasing the oral bioavailability of RPG. Moreover, the NE formulation was more effective than the NP formulation in improving the oral bioavailability of RPG (p < 0.05).

Application of rosemary oil nano-emulsion as antimicrobial and antioxidant natural alternative in pasteurized cream and Karish cheese.

Essential oils possess significant antimicrobial and antioxidant properties and are increasingly used as natural substitutes for food preservation. Therefore, this study investigated the potential application of rosemary essential oil (REO) and REO nano-emulsion in the dairy plant. The antimicrobial effects of REO and REO nano-emulsion were determined by an agar well diffusion assay after chemical profiling by Gas Chromatography-Mass Spectrometry (GC-MS). The REO nano-emulsion was characterized by a Transmission Electron Microscope (TEM). The REO chemical profile revealed the presence of 42 chemical compounds, including 1, 8-cineole (9.72 %), and α-pinene (5.46 %) as major active components. REO nano-emulsion demonstrated significant antimicrobial activity compared to REO (P < 0.05) with a MIC value of 0.0001 mg/ml against Listeria monocytogenes and Aspergillus flavus and 0.001 mg/ml against Pseudomonas aeruginosa and Bacillus cereus. REO nano-emulsion enhanced the oxidative stability of pasteurized fresh cream, revealing a non-significant difference compared with that inoculated with butylated hydroxy anisol (BHA; synthetic antioxidant) (P˃ 0.05). Fortified cream and Karish cheese with REO nano-emulsion were evaluated organoleptically, and the results showed higher grades of overall acceptability when compared to control samples with a statistically significant difference (P < 0.05). Viability studies were estimated using the previously mentioned microorganisms in fortified fresh cream and Karish cheese with REO nano-emulsion. Results of the fortified cream showed a complete reduction of L. monocytogenes, A. flavus, and B. cereus on days 5, 7, and 10, respectively, and a 96.93 % reduction of P. aeruginosa by the end of the storage period. Regarding Karish cheese viability studies, C. albicans, A. flavus, and P. aeruginosa exhibited complete reduction on days 10, 10, and 15 of storage, respectively. In conclusion, REO nano-emulsion was recommended as a natural, safe, and effective antimicrobial and antioxidant additive in the dairy industry.