Anti-Alzheimer Drug Delivery via Pickering Emulsions Stabilized by Plate-like Cellulose Nanocrystals.

In this work, we studied for the first time the formation of olive oil emulsions in water stabilized by plate-like nanocrystals with the supramolecular structure of cellulose II (pCNC). Effects of storage, pCNC concentration, and NaCl on the stability and properties of Pickering emulsions, including the creaming index, droplet size, zeta potential, acid-base surface properties, and rheology, were studied. A significant influence of the shape of nanoparticles (compared to the classical rod-like shape) on the stability parameters and rheological characteristics of emulsions is shown. Plate-like cellulose nanocrystals at a concentration of 16 g/L are able to form delamination-resistant emulsions without added electrolytes. The viscosity of pCNC-stabilized emulsions tends to decrease with increasing electrolyte concentration in the system, which is not characteristic of rod-like CNC-stabilized emulsions. This effect in pCNC-stabilized emulsions assumedly can be associated both with weak mechanical engagement between drops due to the shape of stabilizer particles and with an insignificant participation of background electrolyte cations in the formation of interdroplet interactions. Therefore, the resulting aggregates are unstable and easily destroyed, even under weak mechanical stress. As a consequence, the acid-base properties of the pCNC surface are practically independent of the emulsion preparation method (with or without electrolyte) as well as the concentration of the background electrolyte. The reduced viscosity of pCNC-stabilized emulsions in the presence of an electrolyte, coupled with the absence of acute toxicity, allows us to recommend them as a convenient oral delivery system for fat-soluble, biologically active substances. Our emulsions carrying donepezil (an anti-Alzheimer drug) showed better performance than a solution of donepezil hydrochloride in preventing memory impairment tested on laboratory mice.

Biocompatible Nanoparticle Heteroaggregates as Stabilizers of Pickering Emulsions for Vitamin D3 Efficient Delivery.

Vitamin D3 deficiency is a major public health problem worldwide, and standard cholecalciferol formulations provide poor absorbability of the vitamin. Several biphasic formulas have been proposed to overcome the disadvantages in which Pickering emulsions stand out in particular. This paper describes olive oil-in-water Pickering emulsions stabilized by pseudoboehmite (AlOOH), cellulose nanocrystals (CNC), and their heterocoagulates. Colloidal properties were assessed by laser Doppler microelectrophoresis, potentiometric titration, and rheology. It was shown that the heterocoagulation of CNC and AlOOH led to a drastic change in surface properties (ζ-potential, pKa, and number of active centers), which promoted the formation of more stable emulsions with the smallest size of droplets and the highest viscosity among the studied samples. Simulated digestion studies showed the targeted release in the small intestine medium where cholecalciferol should be delivered. High-performance liquid chromatography showed the efficient encapsulation of cholecalciferol in emulsions (86% of initial concentration). Oral administration to laboratory mice of initial nanoparticles and emulsions stabilized by them showed nontoxicity for all of the components, and they were estimated to be class V materials. The proposed emulsions have great potential as targeted delivery systems of lipophilic drugs.

Surface, rheopexy, digestive stability and toxicity of olive oil emulsions stabilized by chitin nanocrystals for vitamin D3 delivery.

Pickering emulsions are of interest in medicament transport systems. The properties of emulsions are influenced by the type of oil and the surface structure of nanoparticles-stabilizers. The process of formation of o/w emulsions of olive oil stabilized by chitin nanocrystals was investigated, their stability under the influence of physical factors, rheological characteristics, acute toxicity after oral administration, stability under the conditions of a model of the gastrointestinal tract, and their potential for oral transport of vitamin D3 were analyzed. Physically stable emulsions were obtained at a stabilizer concentration of 3.6 g/l. The addition of electrolyte leads to a substantial reduction in the average size of microdroplets. The resulting emulsions have rheopexy properties and the rheopexy index increases at 37 °C. Emulsions are classified as non-toxic when taken orally, physically stable in the upper digestive system, and capable of efficiently transporting vitamin D3 with a full release in the small intestine.

Hemocompatibility, biodegradability and acute toxicity of acetylated cellulose nanocrystals of different types in comparison.

Promotion of promising cellulose nanocrystals (CNC) is largely dependent on the relationship between their morphology, surface chemical composition, and supramolecular structure with toxicity, hemocompatibility, and biodegradability. This paper outlines comparative and integrated analysis of the mentioned biocompatibility aspects of partially acetylated rod-, and disc-lake morphology of CNC with crystalline cellulose allomorphs I and II. These data have also included the study of CNC obtained from the sulfuric acid solutions. The aqueous solution of all types of tested CNC has not been toxic to mice after oral administration. Morphology of internal organs has not changed. However, in case of disc-like particles, the kidney mass coefficient noticeably changed. CNC have neither triggered platelet aggregation nor destroyed the red cell membrane. Intravenous administration to rabbits has not affected the plasma clotting time. Rod-like CNC are more resistant, and the disc-like particles are more susceptible to degradation under the influence of cellulases.

Wrist temperature and cortisol awakening response in humans with social jetlag in the North.

The discrepancy between biological and social rhythms known as social jetlag (SJL) is common in modern society and has a range of negative consequences for cognitive functioning, well-being and health. Social jetlag is typical for people with late chronotypes. As shown earlier, the prevalence of individuals with a late chronotype is higher among the residents of high latitudes. Therefore, a higher rate of detection of people with SJL should be expected in the North. In this study we assessed the detection rate of SJL among 62 young inhabitants of the European North of Russia (the Komi Republic), and the relationship between SJL, the circadian rhythm of the wrist temperature, and the cortisol awakening response (CAR). The detection rate of SJL was 65% among the people examined. A significant decrease in the amplitude (A) of circadian rhythm of wrist temperature: (ß = -0.34 (CI 95%: -0.66 to -0.33); F1,60 = 10.4; p < 0.0001; η(2) = 0.31), an increased incidence of depression: No-SJL = 4.5%; SJL = 17.5% (H = 4.84; p < 0.05), and a tendency for an increase in CAR was also observed in the SJL group. There were sex differences in sensitivity to SJL. Females with SJL but not males had higher global seasonality scores (ß = 0.51 (CI 95%: 0.21 to 0.81); F1,33 = 10.9; p < 0.002; η(2) =0.24), shorter sleep duration (ß = -0.52 (CI 95%: -0.82 to -0.22); F1,33 = 12.9; p < 0.001; η(2) = 0.28), worse sleep quality (ß = 0.39 (CI 95%: 0.07 to 0.72); F1,33 = 6.31; p < 0.017; η(2) = 0.16) and lower A of circadian rhythm of wrist temperature (ß = -0.18 (CI 95%: -0.55 to 0.18); F1,33 = 4.48; p < 0.043; η(2) = 0.13) compared with females without SJL. Thus, our data indicate that 40 of 62 participants of investigation had social jetlag. A decrease of the amplitude of the circadian rhythm of the wrist temperature appears to be an objective marker of SJL. Social jetlag had a strong negative impact on females but not on males.

Abrogation of the oral tolerance to ovalbumin in mice by citrus pectin.

OBJECTIVE: We studied the effects of dietary pectins (citrus pectin [CP] and apple pectin) on oral tolerance in mice. METHODS: Pectins (1 mg/d) were administered orally for 2 wk. Tolerance was induced with 20 mg of ovalbumin (OVA). Levels of serum antibodies (immunoglobulin [Ig] G, IgG1, IgG2a, IgE) and delayed type hypersensitivity response determined in footpad tests were measured after subcutaneous injection of OVA with complete Freund's adjuvant. Concentrations of immunoreactive OVA in blood were measured by enzyme-linked immunosorbent assay after feeding the animals 20 mg of OVA. Adhesion and cytokine production (tumor necrosis factor-alpha, interferon-gamma) were measured in peritoneal macrophages. RESULTS: Oral administration of CP was found to prevent the induction of immune hyporesponsiveness induced by OVA feeding. Animals fed OVA and CP were found to produce similar titers of antigen-specific serum IgG and levels of delayed type hypersensitivity response as those animals not fed OVA. CP increased levels of serum IgG1 and IgE. CP was found to enhance the penetration of immunogenic OVA into the serum. CP (1 mg/d) administered orally for 1 wk was also observed to enhance the adhesion and production of cytokines (tumor necrosis factor-alpha, interferon-gamma) in peritoneal macrophages. CONCLUSION: CP administered orally was shown to inhibit oral tolerance. Enhancement of protein antigen penetration to the blood and activation of macrophages were found to precede the inhibitory effect and appeared to mediate it.

Preventative antiinflammatory effect of potamogetonan, a pectin from the common pondweed Potamogeton natans L.

The pectic polysaccharide named potamogetonan (PN) was obtained using extraction of the leaves and stems of the common pondweed Potamogeton natans L. by an aqueous ammonium oxalate. The purified potamogetonan PN-300 was obtained using membrane ultrafiltration of PN and proved to be pectin with a molecular weight of 300 kDa. The capacity of potamogetonan PN-300 to prevent inflammation was assessed using a carrageenan paw edema test in mice. Oral administration of PN-300 24 h prior to induction of inflammation was found to reduce edema formation in a dose-related manner. The maximal effect of PN-300 was observed at 1 h after carrageenan injection (60% reduction of footpad swelling) and was comparable to that of indomethacin. The delayed edema (5 h) was less affected by pre-administration of PN-300 (33% reduction). PN-300 was found to improve the survival of mice subjected to a lethal dose of LPS. The anti-endotoxemic effect of PN-300 was shown to be mediated by decreased TNF-alpha and IL-1beta and increased IL-10 production.Thus, a pectin named potamogetonan PN-300 was isolated from P. natans and was shown to possess a preventive antiinflammatory effect following oral administration.