Effect of cationic surfactant on the physicochemical and antibacterial properties of colloidal systems (emulsions and microemulsions).

Colloidal systems have been used to encapsulate, protect and release essential oils in mouthwashes. In this study, we investigated the effect of cetylpyridinium chloride (CPC) on the physicochemical properties and antimicrobial activity of oil-in-water colloidal systems containing tea tree oil (TTO) and the nonionic surfactant polysorbate 80. Our main aim was to evaluate whether CPC could improve the antimicrobial activity of TTO, since this activity is impaired when this essential oil is encapsulated with polysorbate 80. These systems were prepared with different amounts of TTO (0-0.5% w/w) and CPC (0-0.5% w/w), at a final concentration of 2% (w/w) polysorbate 80. Dynamic light scattering (DLS) results revealed the formation of oil-swollen micelles and oil droplets as a function of TTO concentration. Increases in CPC concentrations led to a reduction of around 88% in the mean diameter of oil-swollen micelles. Although this variation was of only 20% for the oil droplets, the samples appearance changed from turbid to transparent. The surface charge of colloidal structures was also markedly affected by the CPC as demonstrated by the transition in zeta potential from slightly negative to highly positive values. Electron paramagnetic resonance (EPR) studies showed that this transition is followed by significant increases in the fluidity of surfactant monolayer of both colloidal structures. The antimicrobial activity of colloidal systems was tested against a Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureaus) bacteria. Our results revealed that the inhibition of bacterial growth is observed for the same CPC concentration (0.05% w/w for E. coli and 0.3% w/w for S. aureus) regardless of TTO content. These findings suggest that TTO may not act as an active ingredient in polysorbate 80 containing mouthwashes.

Comparative assessment of emulsifiers for in vitro ruminal gas production and fermentation measurements: Tween 80 is a suitable emulsifier.

Emulsifiers are essential for achieving a homogenous distribution of lipophilic supplements in in vitro rumen fluid incubations. Since emulsifiers can alter rumen fermentation, it is crucial to select one that minimally impacts fermentation parameters to reduce potential biases. This study aimed to evaluate seven emulsifiers' impact on in vitro ruminal fermentation using the Hohenheim Gas Test in order to identify the most inert emulsifier. Rumen fluids were collected from three non-lactating Original Brown-Swiss cannulated cows before morning feeding and incubated for 24 h with a basal diet in triplicates. The emulsifiers tested were ethanol, ethyl acetate, propylene glycol, glycerol, ethylene glycol, soy lecithin, and Tween® 80, each in two dosages (0.5% or 1% v/v). The untreated basal diet served as control. Compared to control, in vitro organic matter digestibility was enhanced by ethyl acetate (by 36.9 and 48.2%), ethylene glycol (by 20.6 and 20.1%), glycerol (by 46.9 and 56.8%) and soy lecithin (by 19.7 and 26.8%) at 0.5 and 1% dosage, respectively. Additionally, the 24-h methane production increased for ethanol (by 41.9 and 46.2%), ethylene glycol (by 50.5 and 51.5%), and glycerol (by 63.1 and 65.4%) for the 0.5 and 1% dosage, respectively, and 0.5% dosage for ethyl acetate (by 31.6%). The acetate molar proportion was 17.2%pt higher for ethyl acetate, and 25.5%pt lower for glycerol at 1% dosage, compared to the control. The propionate concentration was 22.1%pt higher 1% glycerol, and 15.2%pt and 15.1%pt higher for 0.5 and 1% propylene glycol, respectively, compared to the control. In summary, Tween® 80 did not significantly affect in vitro rumen fermentation parameters, making it the most suitable choice for in vitro incubations involving lipophilic substances in rumen fluid. Ethanol may be considered as an alternative emulsifier if methane production is not the variable of interest.

[Preparation and quality evaluation of total flavonoids microemulsion of "Pueraria lobata-Hovenia dulcis"].

The effective components of flavonoids in the "Pueraria lobata-Hovenia dulcis" drug pair have low bioavailability in vivo due to their unstable characteristics. This study used microemulsions with amphoteric carrier properties to solve this problem. The study drew pseudo-ternary phase diagrams through titration compatibility experiments of the oil phase with emulsifiers and co-emulsifiers and screened the prescription composition of blank microemulsions. The study used average particle size and PDI as evaluation indicators, and the central composite design-response surface method(CCD-RSM) was used to optimize the prescription; high-dosage drug-loaded microemulsions were obtained, and their physicochemical properties, appearance, and stability were evaluated. The results showed that when ethyl butyrate was used as the oil phase, polysorbate 80(tween 80) as the surfactant, and anhydrous ethanol as the cosurfactant, the maximum microemulsion area was obtained. When the difference in results was small, K_(m )of 1∶4 was chosen to ensure the safety of the prescription. The prescription composition optimized by the CCD-RSM was ethyl butyrate(16.28%), tween 80(9.59%), and anhydrous ethanol(38.34%). When the dosage reached 3% of the system mass, the total flavonoid microemulsion prepared had a clear and transparent appearance, with average particle size, PDI, and potential of(74.25±1.58)nm, 0.277±0.043, and(-0.08±0.07) mV, respectively. The microemulsion was spherical and evenly distributed under transmission electron microscopy. The centrifugal stability and temperature stability were good, and there was no layering or demulsification phenomenon, which significantly improved the in vitro dissolution of total flavonoids.

Co-encapsulation of hydrophilic and hydrophobic drugs into niosomal nanocarrier for enhanced breast cancer therapy: In silico and in vitro studies.

Combination therapy has been considered one of the most promising approaches for improving the therapeutic effects of anticancer drugs. This is the first study that uses two different antioxidants in full-characterized niosomal formulation and thoroughly evaluates their synergistic effects on breast cancer cells. In this study, in-silico studies of hydrophilic and hydrophobic drugs (ascorbic acid: Asc and curcumin: Cur) interactions and release were investigated and validated by a set of in vitro experiments to reveal the significant improvement in breast cancer therapy using a co-delivery approach by niosomal nanocarrier. The niosomal nanoparticles containing surfactants (Span 60 and Tween 60) and cholesterol at 2:1 M ratio were prepared through the film hydration method. A systematic evaluation of nanoniosomes was carried out. The release profile demonstrated two phases (initial burst followed by sustained release) and a pH-dependent release schedule over 72 h. The optimized niosomal preparation displayed superior storage stability for up to 2 months at 4 °C, exhibiting extremely minor changes in pharmaceutical encapsulation efficiency and size. Free dual drugs (Asc + Cur) and dual-drug loaded niosomes (Niosomal (Asc + Cur)) enhanced the apoptotic activity and cytotoxicity and inhibited cell migration which confirmed the synergistic effect of co-encapsulated drugs. Also, significant up-regulation of p53 and Bax genes was observed in cells treated with Asc + Cur and Niosomal (Asc + Cur), while the anti-apoptotic Bcl-2 gene was down-regulated. These results were in correlation with the increase in the enzyme activity of SOD, CAT, and caspase, and the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) upon treatment with the mentioned drugs. Furthermore, these anti-cancer effects were higher when using Niosomal (Asc + Cur) than Asc + Cur. Histopathological examination also revealed that Niosomal (Asc + Cur) had a lower mitosis index, invasion, and pleomorphism than Asc + Cur. These findings indicated that niosomal formulation for co-delivery of Asc and Cur would offer a promising delivery system for an effective breast cancer treatment.

Small-angle x-ray scattering investigation of the integration of free fatty acids in polysorbate 20 micelles.

A critical quality attribute for liquid formulations is the absence of visible particles. Such particles may form upon polysorbate hydrolysis resulting in release of free fatty acids into solution followed by precipitation. Strategies to avoid this effect are of major interest for the pharmaceutical industry. In this context, we investigated the structural organization of polysorbate micelles alone and upon addition of the fatty acid myristic acid (MA) by small-angle x-ray scattering. Two complementary approaches using a model of polydisperse core-shell ellipsoidal micelles and an ensemble of quasiatomistic micelle structures gave consistent results well describing the experimental data. The small-angle x-ray scattering data reveal polydisperse mixtures of ellipsoidal micelles containing about 22-35 molecules per micelle. The addition of MA at concentrations up to 100 µg/mL reveals only marginal effects on the scattering data. At the same time, addition of high amounts of MA (>500 µg/mL) increases the average sizes of the micelles indicating that MA penetrates into the surfactant micelles. These results together with molecular modeling shed light on the polysorbate contribution to fatty acid solubilization preventing or delaying fatty acid particle formation.

Extensive Characterization of Polysorbate 80 Oxidative Degradation Under Stainless Steel Conditions.

Polysorbate-80 (PS-80) is a common surfactant used in biologics formulations. However, the tendency of oxidation to PS-80 when exposed to stainless steel surfaces brings various challenges during manufacturing processes, such as inconsistent shelf-life of PS-80 solutions, which can further impact the biologics and vaccines production. In this work, the root causes of PS-80 oxidation when in contact with stainless steel conditions were thoroughly investigated through the use of various complementary analytical techniques including U/HPLC-CAD, LC-MS, ICP-MS, peroxide assay, and EPR spectroscopy. The analytical tool kit used in this work successfully revealed a PS-80 degradation mechanism from the perspective of PS-80 content, PS-80 profile, iron content, peroxide production, and radical species. The combined datasets reveal that PS-80 oxidative degradation occurs in the presence of histidine and iron in addition to being combined with the hydroperoxides in PS-80 material. The oxidative pathway and potential degradants were identified by LC-MS. The PS-80 profile based on the U/HPLC-CAD assay provided an effective way to identify early-signs of PS-80 degradation. The results from a peroxide assay observed increased hydroperoxide along with PS-80 degradation. EPR spectra confirmed the presence of histidine-related radicals during PS-80 oxidation identifying how histidine is involved in the oxidation. All assays and findings introduced in this work will provide insight into how PS-80 oxidative degradation can be avoided, controlled, or detected. It will also provide valuable evaluations on techniques that can be used to identify PS-80 degradation related events that occur during the manufacturing process.

Elaboration and characterization of nanoemulsion with orange essential oil and pectin.

BACKGROUND: Nanoemulsions formulated with citric essential oils are currently of interest because of their physical and chemical properties and multiple applications in areas such as the food industry or agrochemicals. These are thermodynamically unstable and have almost Newtonian flow behaviour, but a suitable formulation allows systems to be obtained with good physical stability and rheological properties. The addition of pectin makes this possible. In this work, food nanoemulsions formulated with pectin, orange essential oil (5 wt%), and Tween 80 were obtained by microfluidization. First, the effect of Tween 80 concentration from 1 to 5 wt% on emulsions without pectin was evaluated. Then, pectin was added to the most stable nanoemulsion obtained and two variables were studied: the pectin solution concentration (from 2 to 6 wt%) and the pectin/emulsion ratio (1:1 or 2:1) at a fixed pectin concentration. RESULTS: Rheological, laser diffraction, and multiple light scattering techniques were employed to determine the content of Tween 80 that results in the most stable nanoemulsion without pectin, which was 3 wt%. In addition, these techniques were used to determine the structure and physical stability of the nanoemulsions containing orange essential oil and pectin. The results obtained showed that the emulsions containing 2 wt% pectin were destabilized before 24 h. Furthermore, the emulsion with 6 wt% pectin and a 2:1 pectin/emulsion ratio showed the highest viscosity and the lowest mean diameters, and therefore the greatest stability. CONCLUSION: This work extends the knowledge of formulation of nanoemulsions and using essential oils. © 2021 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Nanoemulsions containing Garcinia mangostana L. pericarp extract for topical applications: Development, characterization, and in vitro percutaneous penetration assay.

A highly stable oil-in-water nanoemulsion for topical applications, containing mangostins extracted from the pericarp of mangosteen (Garcinia mangostana L.), is a promising strategy to protect mangostins as well as to improve penetration of these important antioxidants through the skins. Nanoemulsions consisted of virgin coconut oil as the oil phase, Tween-80 and Span-80 as surfactants, and xanthan gum as the thickening agent, were prepared using the high-energy and low-energy emulsification methods. The nanoemulsions that were stable up to 28 days had oil droplet diameter of 220 nm to 353 nm and zeta potential of -46.9 mV to -63.7 mV. The accelerated stability test showed that the most stable nanoemulsions were those prepared using the low-energy emulsification method with an estimated shelf life of eleven months, composed of 11% oil phase, 17% surfactant, and 72% aqueous phase. The in vitro percutaneous penetration test for the nanoemulsion with added xanthan gum provided high cumulative skin penetration of mangostins of up to 114 µg/cm2. The results of this study indicate that virgin coconut oil-based nanoemulsions containing mangostins, prepared using the low-energy emulsification method, stabilized by xanthan gum and mixed at 40°C can prospectively be used for topical applications.

Effects of Surfactant Volume Fraction on the Antioxidant Efficiency and on The Interfacial Concentrations of Octyl and Tetradecyl p-Coumarates in Corn Oil-in-Water Emulsions.

Surfactants have been used for decades in the food industry for the preparation of lipid-based emulsified food stuffs. They play two main roles in the emulsification processes: first they decrease the interfacial tension between the oil and water, facilitating droplet deformation and rupture; second, they reduce droplet coalescence by forming steric barriers. However, addition of surfactants to binary oil-water mixtures also brings up the formation of three-dimensional interfacial layers, surrounding each emulsion droplet, that significantly alter chemical reactivity. This is the case, for instance, in the inhibition reaction between antioxidants and the lipid radicals formed in the course of the spontaneous oxidation reaction of unsaturated lipids, which are commonly employed in the preparation of food-grade emulsions. The rate of the inhibition reaction depends on the effective concentrations of antioxidants, which are mostly controlled by the amount of surfactant employed in the preparation of the emulsion. In this work, we analyze the effects of the surfactant Tween 20 on the oxidative stability and on the effective concentrations of two model antioxidants derived from cinnamic acid, determining their interfacial concentrations in the intact emulsions to avoid disrupting the existing equilibria and biasing results. For this purpose, a recently developed methodology was employed, and experimental results were interpreted on the grounds of a pseudophase kinetic model.

New potential application of hydroxypropyl-ß-cyclodextrin in solid self-nanoemulsifying drug delivery system and solid dispersion.

The purpose of this study was to use hydroxypropyl-ß-cyclodextrin (HP-ß-CD) as a novel carrier in solid SNEDDS and solid dispersions to enhance the solubility and oral bioavailability of poorly water-soluble dexibuprofen. The novel dexibuprofen-loaded solid SNEDDS was composed of dexibuprofen, corn oil, polysorbate 80, Cremophor® EL, and HP-ß-CD at a weight ratio of 45/35/50/15/100. This solid SNEDDS spontaneously formed a nano-emulsion with a size of approximately 120 nm. Unlike the conventional solid SNEDDS prepared with colloidal silica as a carrier, this dexibuprofen-loaded solid SNEDDS exhibited a spherical structure. Similar to the dexibuprofen-loaded solid dispersion prepared with HP-ß-CD, the transformation of the crystalline drug to an amorphous state with no molecular interactions were observed in the solid SNEDDS. Compared to the solid dispersion and dexibuprofen powder, solid SNEDDS significantly enhanced drug solubility and AUC. Therefore, HP-ß-CD is a novel potential carrier in SNEDDS for improving the oral bioavailability of dexibuprofen.

Structure and Fate of Nanoparticles Designed for the Nasal Delivery of Poorly Soluble Drugs.

Nanoparticles are promising mediators to enable nasal systemic and brain delivery of active compounds. However, the possibility of reaching therapeutically relevant levels of exogenous molecules in the body is strongly reliant on the ability of the nanoparticles to overcome biological barriers. In this work, three paradigmatic nanoformulations vehiculating the poorly soluble model drug simvastatin were addressed: (i) hybrid lecithin/chitosan nanoparticles (LCNs), (ii) polymeric poly-ε-caprolactone nanocapsules stabilized with the nonionic surfactant polysorbate 80 (PCL_P80), and (iii) polymeric poly-ε-caprolactone nanocapsules stabilized with a polysaccharide-based surfactant, i.e., sodium caproyl hyaluronate (PCL_SCH). The three nanosystems were investigated for their physicochemical and structural properties and for their impact on the biopharmaceutical aspects critical for nasal and nose-to-brain delivery: biocompatibility, drug release, mucoadhesion, and permeation across the nasal mucosa. All three nanoformulations were highly reproducible, with small particle size (∼200 nm), narrow size distribution (polydispersity index (PI) < 0.2), and high drug encapsulation efficiency (>97%). Nanoparticle composition, surface charge, and internal structure (multilayered, core-shell or raspberry-like, as assessed by small-angle neutron scattering, SANS) were demonstrated to have an impact on both the drug-release profile and, strikingly, its behavior at the biological interface. The interaction with the mucus layer and the kinetics and extent of transport of the drug across the excised animal nasal epithelium were modulated by nanoparticle structure and surface. In fact, all of the produced nanoparticles improved simvastatin transport across the epithelial barrier of the nasal cavity as compared to a traditional formulation. Interestingly, however, the permeation enhancement was achieved via two distinct pathways: (a) enhanced mucoadhesion for hybrid LCN accompanied by fast mucosal permeation of the model drug, or (b) mucopenetration and an improved uptake and potential transport of whole PCL_P80 and PCL_SCH nanocapsules with delayed boost of permeation across the nasal mucosa. The correlation between nanoparticle structure and its biopharmaceutical properties appears to be a pivotal point for the development of novel platforms suitable for systemic and brain delivery of pharmaceutical compounds via intranasal administration.

Development, Characterization, and Immunomodulatory Evaluation of Carvacrol-loaded Nanoemulsion.

Carvacrol (CV) is an essential oil with numerous therapeutic properties, including immunomodulatory activity. However, this effect has not been studied in nanoemulsion systems. The objective of this study was to develop an innovative carvacrol-loaded nanoemulsion (CVNE) for immunomodulatory action. The developed CVNE comprised of 5% w/w oily phase (medium chain triglycerides + CV), 2% w/w surfactants (Tween 80®/Span 80®), and 93% w/w water, and was produced by ultrasonication. Dynamic light scattering over 90 days was used to characterize CVNE. Cytotoxic activity and quantification of cytokines were evaluated in peripheral blood mononuclear cell (PBMC) culture supernatants. CVNE achieved a drug loading of 4.29 mg/mL, droplet size of 165.70 ± 0.46 nm, polydispersity index of 0.14 ± 0.03, zeta potential of -10.25 ± 0.52 mV, and good stability for 90 days. CVNE showed no cytotoxicity at concentrations up to 200 µM in PBMCs. CV diminished the production of IL-2 in the PBMC supernatant. However, CVNE reduced the levels of the pro-inflammatory cytokines IL-2, IL-17, and IFN-γ at 50 µM. In conclusion, a stable CVNE was produced, which improved the CV immunomodulatory activity in PBMCs.

Preparation of Catechin Nanoemulsion from Oolong Tea Leaf Waste and Its Inhibition of Prostate Cancer Cells DU-145 and Tumors in Mice.

Anti-cancer activity of catechin nanoemulsions prepared from Oolong tea leaf waste was studied on prostate cancer cells DU-145 and DU-145-induced tumors in mice. Catechin nanoemulsions composed of lecithin, Tween-80 and water in an appropriate proportion was prepared with high stability, particle size of 11.3 nm, zeta potential of -67.2 mV and encapsulation efficiency of 83.4%. Catechin nanoemulsions were more effective than extracts in inhibiting DU-145 cell growth, with the IC50 being 13.52 and 214.6 µg/mL, respectively, after 48 h incubation. Furthermore, both catechin nanoemulsions and extracts could raise caspase-8, caspase-9 and caspase-3 activities for DU-145 cell apoptosis, arresting the cell cycle at S and G2/M phases. Compared to control, catechin nanoemulsion at 20 µg/mL and paclitaxel at 10 µg/mL were the most effective in reducing tumor volume by 41.3% and 52.5% and tumor weight by 77.5% and 90.6% in mice, respectively, through a decrease in EGF and VEGF levels in serum.

Physical and turbidimetric properties of cholecalciferol- and menaquinone-loaded lipid nanocarriers emulsified with polysorbate 80 and soy lecithin.

The present study aimed to investigate the physical and turbidimetric properties of cholecalciferol- and menaquinone-loaded lipid nanocarriers emulsified with different ratios of polysorbate 80 and soy lecithin. The lipid nanocarriers were subjected to three different heat treatments, LTLT (low temperature long time), HTST (high temperature short time), and autoclave treatments. Both cholecalciferol and menaquinone were successfully encapsulated in lipid nanocarriers and there was little loss of them during preparation. The droplet size of lipid nanocarriers emulsified with only polysorbate 80 increased and its PDI became larger than 0.3 after autoclave treatment. Moreover, 30.9% and 49.4% of cholecalciferol and menaquinone, respectively, were lost. In turbidimetric analysis, the destabilization by creaming formation in the upper layer of the lipid nanocarriers emulsified with a high polysorbate ratio was observed. However, the use of combination of both emulsifiers inhibited destabilization by flocculation as well as retained the cholecalciferol and menaquinone after all heat treatments.

Formation and Stabilization of W1/O/W2 Emulsions with Gelled Lipid Phases.

Water-in-oil-in-water (W1/O/W2) emulsions are emulsion-based systems where the dispersed phase is an emulsion itself, offering great potential for the encapsulation of hydrophilic bioactive compounds. However, their formation and stabilization is still a challenge mainly due to water migration, which could be reduced by lipid phase gelation. This study aimed to assess the impact of lipid phase state being liquid or gelled using glyceryl stearate (GS) at 1% (w/w) as well as the hydrophilic emulsifier (T80: Tween 80 or lecithin) and the oil type (MCT:medium chain triglyceride or corn oil (CO) as long chain triglyceride) on the formation and stabilization of chlorophyllin W1/O/W2 emulsions. Their colloidal stability against temperature and light exposure conditions was evaluated. Gelling both lipid phases (MCT and CO) rendered smaller W1 droplets during the first emulsification step, followed by formation of W1/O/W2 emulsions with smaller W1/O droplet size and more stable against clarification. The stability of W1/O/W2 emulsions was sensitive to a temperature increase, which might be related to the lower gelling degree of the lipid phase at higher temperatures. This study provides valuable insight for the formation and stabilization of W1/O/W2 emulsions with gelled lipid phases as delivery systems of hydrophilic bioactive compounds under common food storage conditions.

Associating chitosan and microemulsion as a topical vehicle for the administration of herbal medicines.

A viscous solution of low molecular weight chitosan (CH) at 5% w/v (10.2 kDa, 75 % deacetylated, 1451 cP at 25 °C) was associated with a microemulsion (ME) that undergoes a phase transition after water absorption in situ (≈28 % w/w), forming a more viscous liquid crystal, which was potentially evaluated as a topical vehicle. The ME was selected from a phase diagram, selecting a composition based on Tween® 80 (52 %), myristate isopropyl (28 %), and the aqueous phase (water and polyethylene glycol 400, 60:40 w/w) (20 %), which was after replaced by CH and herbal medicines (HM). HM are alternatives to treat candidiasis, and Stryphnodendron adstringens shell extract, characterized by molecular networking, and Melaleuca alternifolia Chell essential oil (46 % of terpinen-4-ol), showed in vitro activity against Candida albicans. Associating CH in ME improved the mechanical properties of the topical formulation, as adhesiveness, which is an advantageous feature for the topical treatment of vulvovaginal candidiasis.

Water-in-Oil-in-Water Nanoemulsions Containing Temulawak (Curcuma xanthorriza Roxb) and Red Dragon Fruit (Hylocereus polyrhizus) Extracts.

Hydrophobic curcumin in temulawak extract and hydrophilic betacyanin in red dragon fruit extract are high-value bioactive compounds with extensive applications in functional food. In this study, these extracts were encapsulated in water-in-oil-in-water (w/o/w) nanoemulsions as a delivery system using a two-step high-energy emulsification method. PGPR and Span 20 were used as lipophilic emulsifiers for the primary w/o emulsion. The most stable w/o/w formulation with the least oil phase separation of 5% v/v consisted of w/o emulsion (15% w/w) and Tween 80 (1.5% w/w) as hydrophilic emulsifier. The formulation was characterized by a 189-nm mean droplet diameter, 0.16 polydispersity index, and -32 mV zeta potential. The freeze-thaw stability may be attributed to the combination of low w/o emulsion content and high Tween 80 concentration in the outer water phase of the w/o/w nanoemulsions used in this study. The IC50 values of the nanoemulsion and the red dragon fruit extract were similar. It means that the higher concentration of curcumin in the nanoemulsions and the lower IC50 value of temulawak extract ensured sufficient antioxidant activities of the w/o/w nanoemulsions.

Interactions of ß-carotene with WPI/Tween 80 mixture and oil phase: Effect on the behavior of O/W emulsions during in vitro digestion.

This study investigated the impact of adding ß-carotene on the structure of fresh O/W emulsions with different oil phase (sunflower oil-LCT or NEOBEE®1053-MCT) and emulsifiers (WPI, Tween 80 - T80 or WPI/T80 mixture). In this sense, the behavior of emulsions through the gastrointestinal tract, the stability and bioaccessibility of ß-carotene were also assessed. The ß-carotene reduced the interfacial tension of the LCT/MCT-water systems. The addition of ß-carotene promoted an increase of viscoelasticity of LCT/MCT-T80 (0.5%WPI/0.5%T80 and 1%T80 w/w) interfaces, but an increase of WPI content reduced the viscoelasticity of interfacial layers (LCT/MCT-1% WPI). These changes in the interface properties influenced the mean droplet size and ζ-potential of the fresh emulsions. LCT systems presented similar bioaccessibility/stability of ß-carotene. However, ß-carotene entrapped within protein-coated MCT droplets was more stable than within T80-MCT systems. Our results show that ß-carotene interacted with other ingredients of emulsions changing their properties and behavior under gastrointestinal tract as well as the stability/bioaccessibility of ß-carotene.

Development of an Orally Bioavailable Isoliquiritigenin Self-Nanoemulsifying Drug Delivery System to Effectively Treat Ovalbumin-Induced Asthma.

PURPOSE: Isoliquiritigenin (ILQ), an important component of Anti-Asthma Herbal Medicine Intervention (ASHMI), had shown potent anti-asthma effect in vitro in our previous study. However, poor solubility and low bioavailability hindered in vivo application to treat asthma. This study was to develop a novel ILQ loaded self-nanoemulsifying drug delivery system (ILQ-SMEDDS) with enhanced bioavailability. METHODS: The optimized SMEDDS formulation was composed of ethyl oleate (oil phase), Tween 80 (surfactant) and PEG400 (co-surfactant) at a mass ratio of 3:6:1. The physiochemical properties of ILQ-SMEDDS, including drug content, globule size, zeta potential, scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, were characterized. And the in vitro release profile, in situ intestinal absorption, in vivo pharmacokinetic parameters and the anti-asthma effect of ILQ suspension and ILQ-SMEDDS were evaluated. RESULTS: The ILQ-SMEDDS had an average globule size of 20.63 ± 1.95 nm with a polydispersity index (PDI) of 0.11 ± 0.03, and its zeta potential was -12.64 ± 2.12 mV. The cumulative release rate of ILQ from ILQ-SMEDDS to the simulated gastrointestinal tract was significantly higher than that of free ILQ suspension. And area under curve with ILQ-SMEDDS was found to be 3.95 times higher than that of ILQ suspension indicating improved bioavailability by SMEDDS. Although ILQ-SMEDDS showed a slight less effective inhibitory effect on eotaxin-1 in human lung fibroblast (HFL-1) cells than free ILQ, in an ovalbumin-induced asthma model, ILQ-SMEDDS exhibited more efficacy than ILQ suspension in improving asthma-associated inflammation, including eosinophil production, ovalbumin-specific immunoglobulin E (OVA-sIgE), interleukin 4 (IL 4), interleukin 5 (IL 5) and interferon-γ (IFN-γ). Even the low dose of ILQ-SMEDDS group (10 mg/kg) showed better anti-asthma effect than that of the ILQ suspension group (20 mg/kg). CONCLUSION: Compared with ILQ suspension, ILQ-SMEDDS showed significantly improved bioavailability and anti-asthma effect, revealing its potential as a favorable pharmaceutical agent for treating asthma.

Quality by Design Approach for Preparation of Zolmitriptan/Chitosan Nanostructured Lipid Carrier Particles - Formulation and Pharmacodynamic Assessment.

PURPOSE: Zolmitriptan (ZT) is a selective serotonin agonist that is used for the treatment of migraine. It belongs to BCS class III with high solubility and low permeability. Besides, the drug is subjected to pre-systemic metabolism. Accordingly, new Zolmitriptan/chitosan nanostructured lipid carriers (ZT/CT NLCs) coated with Tween 80 (stealthy layer) have been developed to overcome such demerits. METHODS: The NLCs were developed by combining ultrasonication and double emulsion (w/o/w) techniques. The lipids were Gelucire and Labrasol. Herein, the quality by design (23 full factorial design) was scrupulously followed, where critical process parameters and critical quality attributes were predefined. The optimized formulation (F8) was fully characterized with respect to entrapment efficiency (%EE), percentage yield (% yield), particle size, size distribution (PDI), zeta potential (ZP), morphological appearance (TEM). In vitro release, stability study and pharmacodynamic evaluations were also assessed. The optimized freeze dried formula was dispensed in in situ gelling hard gelatin capsule encompassing pectin and guar gum for further in vitro and pharmacodynamic evaluations. RESULTS: The optimized spherical nanoparticles experienced high percentage EE and yield (78.14% and 60.19%, respectively), low particle size and PDI (343.87 nm and 0.209, respectively), as well as high negative ZP (-25.5 mV). It showed good physical stability at refrigerated conditions. The NLCs dispensed in in situ gelling hard gelatin capsule comprising pectin and guar gum experienced sustained release for 30 h and significantly maintained the pharmacological effect in mice up to 8 h (p < 0.001). CONCLUSION: ZT, a BCS class III drug that suffers from poor permeability and pre-systemic metabolism, was successfully maneuvered as nanostructured lipid carrier particles (NLCs). The incorporation of the NLCs in in situ gelling hard gelatin capsules fulfilled a dual function in increasing permeability, as well as sustaining the pharmacodynamic effect. This result would open new vistas in improving the efficacy of other class III drugs.