The long-term biodistribution of non-biodegradable microstructures or nanostructures used in vaccinations is widely unknown. This is the case for aluminum oxyhydroxide, the most widely used vaccine ...adjuvant, which is a nanocrystalline compound that spontaneously forms nanoprecipitates. Although generally well-tolerated, aluminum oxyhydroxide is detected in macrophages a long time after vaccination in individuals predisposed to the development of systemic and neurological aspects of the autoimmune (inflammatory) syndrome induced by modified adjuvant. In the present study, we established that the terminal sterilization of aluminum oxyhydroxide by autoclaving in final container vials produced measurable changes in its physicochemical properties. Moreover, we found that these changes included (1) a decreasing in the pH of aluminum oxyhydroxide solutions, (2) a reduction in the adsorption capacity of bovine serum albumin, (3) a shift in the angle of X-ray diffraction, (4) a reduction in the lattice spacing, causing the crystallization and biopersistence of modified aluminum oxyhydroxide in the macrophage, as well as in muscle and the brain.
Abstract Objective The ω-3 polyunsaturated fatty acid therapy in inflammatory bowel disease is focused on the effects on fish oil–derived polyunsaturated fatty acids. We speculated that a vegetal oil ...rich in α-linolenic acid (ALA) might also inhibit colitis. Therefore, we evaluated whether dietary ALA would decrease the expression of adhesion molecules by inducing the protective enzyme heme oxygenase-1 (HO-1) in a rat colitis model. Methods Colitis was induced at day 0 by an intrarectal injection of 2-4-6-trinitrobenzen sulfonic acid (TNBS), whereas control rats received the vehicle. Rats were fed an ALA-rich formula 450 mg · kg−1 · d−1 , whereas the other colitic group (TNBS) and the control group were fed an isocaloric corn oil formula for 14 d (from day −7 to day 7). The colonic expressions of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), vascular endothelial growth factor A receptor-2 (VEGFR2), and HO-1 were studied by immunohistochemistry. Results The ALA-rich diet significantly decreased the expression of ICAM-1, VCAM-1, and VEGFR-2 compared the TNBS group, but it did not affect the expression of HO-1. Conclusion A vegetal ALA-rich formula decreases the expression of ICAM-1, VCAM-1, and VEGFR-2 and independently of HO-1 in rats with TNBS-induced colitis. Further studies are required to evaluate its therapeutic potential in inflammatory bowel disease as an alternative to fish oil.
A novel polymer synthesized by grafting three cyclodextrins onto chitosan was characterized and evaluated for its potential to adsorb two pharmaceutical residues: ibuprofen and progesterone. The ...influence of various operational parameters, including contact time, initial molecule concentration, pH, ionic strength, and temperature, was investigated. The synthesized polymer exhibits an amorphous and porous structure with a remarkable swelling capacity of 9.5 mmol/g. It demonstrates remarkable adsorption capacities for progesterone and ibuprofen, reaching 90% and 75%, respectively. Kinetic studies reveal that the adsorption of both molecules follows a pseudo-second-order model. A DSC analysis elucidated the adsorption mechanism, which is governed by the formation of inclusion complexes and electrostatic interactions within the polymer network. The polymer’s regeneration after 23 cycles demonstrates its sustainable adsorption efficiency. The combination of chitosan with three cyclodextrins opens up promising new avenues for water treatment and the removal of specific pollutants. This approach significantly improves the material’s selectivity towards target pollutants, offering a significant advantage in pollution remediation applications.
A batch system was applied to study the adsorption of three dyes (methyl violet, eriochrom black T and helianthin) from aqueous solution onto β-cyclodextrin polymer, synthesized by using citric acid ...as a cross linking agent. This polymer lets to adsorb only methyl violet for this effect, several operator variables was checked only with this kind of dye, the removal efficiently increases with increase in adsorbent amount; elevation of temperature lets also to improve the dye adsorption; ionic strength has not effect on dye adsorption process, for the pH we have remarked a slight decrease in removal efficiently with increasing of pH values. Equilibrium study was investigated by applying three models (Langumir, Frendlich and Temkin), results show that Langumir isotherm is the appropriate model. FTIR spectra show the complex inclusion formation which dominates the adsorption mechanism, confirmed by the absence of characteristic peaks of methyl violet in ß-cyclodextrin after adsorption.
Direct nose-to-brain delivery has been raised as a non-invasive powerful strategy to deliver drugs to the brain bypassing the blood-brain barrier (BBB). This study aimed at preparing and ...characterizing an innovative composite formulation, associating the liposome and hydrogel approaches, suitable for intranasal administration. Thermosensitive gel formulations were obtained based on a mixture of two hydrophilic polymers (Poloxamer 407, P407 and Poloxamer 188, P188) for a controlled delivery through nasal route via liposomes of an active pharmaceutical ingredient (API) of potential interest for Alzheimer's disease. The osmolarity and the gelation temperature (T° sol-gel) of formulations, defined in a ternary diagram, were investigated by rheometry and visual determination. Regarding the issue of assays, a mixture composed of P407/P188 (15/1%,
) was selected for intranasal administration in terms of T° sol-gel and for the compatibility with the olfactory mucosal (280 ± 20 mOsmol, pH 6). Liposomes of API were prepared by the thin film hydration method. Mucoadhesion studies were performed by using mucin disc, and they showed the good natural mucoadhesive characteristics of in situ gel formulations, which increased when liposomes were added. The study demonstrated successful pharmacotechnical development of a promising API-loaded liposomes in a thermosensitive hydrogel intended for nasal Alzheimer's disease treatment
We have previously shown that α-linolenic acid (ALA), a (n-3) PUFA exerts in vitro antiinflammatory effects in the intestine. In this study, we aimed to evaluate its effect on inflammatory and ...oxidative stress in a colitis model. Colitis was induced in 2 groups at d 0 by intrarectal injection of 2-4-6-trinitrobenzen sulfonic acid (TNBS), whereas the control group received the vehicle. Rats we fed 450 mg·kg⁻¹·d⁻¹ of ALA (TNBS+ALA) while the other colitic group (TNBS) and the control group were fed an isocaloric corn oil formula for 14 d (from d -7 to d 7). RBC fatty acid composition was assessed. Oxidative stress was studied by measuring urinary 8-isoprostanes (8-IP) and colon glutathione (GSH) concentration and inducible nitric oxide synthase (iNOS) expression. Colitis was assessed histologically, by production of proinflammatory mediators, including cytokines, leukotrienes B₄ (LTB₄), and cyclooxygenase-2 (COX-2) and by nuclear factor-κB (NF-κB) activation. The ALA-rich diet significantly increased the RBC levels of ALA, eicosapentaenoic acid, and docosapentaenoic acid (n-3) compared with the TNBS group (P < 0.01 for all). The beneficial effect of ALA supplementation on oxidative stress was reflected by lower urinary 8-IP levels (P < 0.05), a normalized colon GSH concentration (P < 0.01), and reduced colon iNOS expression (P < 0.05) compared with the TNBS group. ALA also protected against colon inflammation as assessed by lower tumor necrosis factor-α secretion and mRNA level (P < 0.05), reduced NF-κB activation (P = 0.01), and lower colon lipid mediator concentrations such as LTB₄ and COX-2 (P < 0.05) compared with the TNBS group. These findings show that an ALA-rich formula is beneficial to TNBS-induced colitic rats via inhibition of oxidative and inflammatory stress.
ABSTRACT
This contribution focused on the solubility improvement of the poorly water-soluble steroid hormone progesterone which, in its natural state, presents a reduced oral bioavailability. In the ...first part of this study, two simple, reproducible methods that were candidates for use in the preparation of inclusion complexes with cyclodextrins were investigated. Solubility capacities of the progesterone complex with hydroxypropyl- -CD (HP -CD), hydoxypropyl- -CD (HP -CD), permethyl- -CD (PM -CD), and sulfobutylether- -CD (SBE -CD), prepared by the freeze-drying and precipitation methods, were evaluated by Higuchi phase solubility studies. The results showed that HP -CD and PM -CD were the most efficient among the four cyclodextrins for the solubilization of progesterone, with the highest apparent stability constants. Therefore, dissolution studies were conducted on these latest progesterone/cyclodextrin complexes and physical mixtures. Two additional natural cyclodextrins, -CD and -CD, were taken as references. Hence, the influence of more highly soluble derivatives of -CD (HP -CD, PM -CD) on the progesterone dissolution rate, in comparison to pristine -CD, alongside an increase in the cavity width for -CD versus -CD, were investigated. The dissolution kinetics of progesterone dissolved from HP -CD, PM -CD, and -CD revealed higher constant rates in comparison to -CD. Therefore, the aim of the second part of this study was to investigate the possibility of improving the dissolution rate of progesterone/ -CD binary systems upon formation of ternary complexes with the hydrophilic polymer, PEG 6000, as -CD had the smallest progesterone solubility and dissolution capacity among the four cyclodextrins studied ( -CD, HP -CD, HP -CD and PM -CD). The results indicated that dissolution constant rates were considerably enhanced for the 5% and 10% progesterone/ -CD complexes in PEG 6000.
The interaction of progesterone with the cyclodextrins of interest on the form of the binary physical mixtures, complexes, or ternary complexes were investigated by differential scanning calorimetry (DSC) and Fourier transformed-infrared spectroscopy (FT-IR). The results proved that progesterone was diffused into the cyclodextrin cavity, replacing the water molecules and, in case of ternary systems, that the progesterone -cyclodextrin was well dispersed into PEG, thus improving progesterone bioavailability for subsequent oral delivery in the same way as derivatized cyclodextrins. The present work proves that ternary complexes are promising systems for drug encapsulation.
The effects of a dietary supplementation with the vegetable ω-3 α-linolenic acid (ALA) on cardiovascular homeostasis are unclear. In this context, it would be interesting to assess the effects of ...camelina oil.
This study aimed to assess the cardiovascular and metabolic effects of camelina oil in hypertensive patients with metabolic syndrome.
In a double-blind, placebo-controlled randomized study, treated essential hypertensive patients with metabolic syndrome received, during 6 mo, either cyclodextrin-complexed camelina oil containing ≈ 1.5 g ALA/d (n = 40) or an isocaloric placebo (n = 41), consisting of the same quantity of cyclodextrins and wheat starch. Anthropometric data, plasma lipids, glycemia, insulinemia, creatininemia, TBARs, high-sensitivity C-reactive protein, and n–3, n–6, and n–9 fatty acids in erythrocyte membranes were measured. Peripheral and central blood pressures, arterial stiffness, carotid intima-media thickness, and brachial artery endothelium-dependent flow-mediated dilatation (FMD) and endothelium-independent dilatation were assessed.
Compared with placebo, camelina oil increased ALA (mean ± SD: 0 ± 0.04 compared with 0.08 ± 0.06%, P <0.001), its elongation product EPA (0 ± 0.5 compared with 0.16 ± 0.65%, P <0.05), and the n–9 gondoic acid (GA; 0 ± 0.04 compared with 0.08 ± 0.04%, P <0.001). No between-group difference was observed for cardiovascular parameters. However, changes in FMD were associated with the magnitude of changes in EPA (r = 0.26, P = 0.03). Compared with placebo, camelina oil increased fasting glycemia (–0.2 ± 0.6 compared with 0.3 ± 0.5 mmol/L, P <0.001) and HOMA-IR index (–0.8 ± 2.5 compared with 0.5 ± 0.9, P <0.01), without affecting plasma lipids, or inflammatory and oxidative stress markers. Changes in HOMA-IR index were correlated with the magnitude of changes in GA (r = 0.32, P <0.01). Nutritional intake remained similar between groups.
ALA supplementation with camelina oil did not improve vascular function but adversely affected glucose metabolism in hypertensive patients with metabolic syndrome. Whether this adverse effect on insulin sensitivity is related to GA enrichment, remains to be elucidated.
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Solar radiation is classified as a known human carcinogen. In France, people frequently ask local pharmacies to dispense products for sunburns. In the PRISME project, studying this use can be a ...specific and sensitive way to assess these overexposures.
This study aims to construct an indicator for monitoring healthcare consumption in pharmacies after overexposure to solar UV.
The study, conducted between July and August 2019, covered a sample of pharmacies located in coastal communities of southern France. A list of products for sunburn was defined. When one of the products on this list was sold, the customer was asked to fill out a questionnaire to determine whether the purchase was related to UV overexposure. A positive predictive value (PPV) per active ingredient was calculated.
Overall, nine pharmacies participated in the study, and 288 questionnaires were collected. The majority of products purchased were for women (60.7%), for people aged 15 and over (78.1%), and for people not living in the department (68.9%). The most frequently purchased products were our trolamine-containing products which accounted for 53% of sales. With the exception of three products, all PPVs were greater than 0.8.
The high PPV confirms the suitability of the product selection as an indicator for monitoring healthcare consumption related to solar UV overexposure. Two indicators (one sensitive and one specific) were selected to maximise the chances of identifying UV-related remedies.
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