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Journal of Environmental Sciences... Aug 2021Polyaluminum chloride modified clay (PAC-MC) is a safe and efficient red tide control agent that has been studied and applied worldwide. Although it is well known that...
Polyaluminum chloride modified clay (PAC-MC) is a safe and efficient red tide control agent that has been studied and applied worldwide. Although it is well known that the distribution of hydrolytic aluminum species in PAC affects its flocculation, little is known about the influence of particulars aluminum species on the microalgae removal efficiency of PAC-MC; this lack of knowledge creates a bottleneck in the development of more efficient MCs based on aluminum salts. The ferron method was used in this study to quantitatively analyze the distributions of and variations in different hydrolytic aluminum species during the process of microalgae removal by PAC-MC. The results showed that Al, which made up 5%-20% of the total aluminum, and Al, which made up 15%-55% of the total aluminum, significantly affected microalgae removal, with Pearson's correlation coefficients of 0.83 and 0.89, respectively. Most of the aluminum in the PAC-MC sank rapidly into the sediments, but the rate and velocity of settlement were affected by the dose of modified clay. The optimal dose of PAC-MC for precipitating microalgae was determined based on its aluminum profile. These results provide guidance for the precise application of PAC-MC in the control of harmful algal blooms.
Topics: Aluminum; Aluminum Hydroxide; Clay; Flocculation; Microalgae
PubMed: 34210441
DOI: 10.1016/j.jes.2021.01.008 -
Journal of Pharmaceutical Sciences Jun 2018Adjuvants are necessary to enable vaccine development against a significant number of challenging pathogens for which effective vaccines are not available. We engineered...
Adjuvants are necessary to enable vaccine development against a significant number of challenging pathogens for which effective vaccines are not available. We engineered a novel small-molecule immune potentiator, a benzonaphthyridine agonist targeting toll-like receptor 7 (TLR7), as a vaccine adjuvant. TLR7 agonist (TLR7a) was engineered to be adsorbed onto aluminum hydroxide (AlOH), and the resulting AlOH/TLR7a was evaluated as a vaccine adjuvant. AlOH/TLR7a exploits the flexibility of AlOH formulations, has an application in many vaccine candidates, and induced good efficacy and safety profiles against all tested antigens (bacterial- and viral-derived protein antigens, toxoids, glycoconjugates, and so forth) in many animal models, including nonhuman primates. In this article, we describe the outcome of the physicochemical characterization of AlOH/TLR7a. Reverse-phase ultra performance liquid chromatography, confocal microscopy, flow cytometry, zeta potential, and phosphophilicity assays were used as tools to demonstrate the association of TLR7a to AlOH and to characterize this novel formulation. Raman spectroscopy, nuclear magnetic resonance, and mass spectroscopy were also used to investigate the interaction between TLR7a and AlOH (data not shown). This pivotal work paved the way for AlOH/TLR7a to progress into the clinic for evaluation as an adjuvant platform for vaccines against challenging preventable diseases.
Topics: Adjuvants, Immunologic; Adsorption; Aluminum Hydroxide; Animals; Humans; Naphthyridines; Toll-Like Receptor 7
PubMed: 29421216
DOI: 10.1016/j.xphs.2018.01.024 -
Vaccine Sep 2023The ongoing evolution and emergence of SARS-CoV-2 variants have raised concerns regarding the efficacy of existing vaccines and therapeutic agents. This study aimed to...
The ongoing evolution and emergence of SARS-CoV-2 variants have raised concerns regarding the efficacy of existing vaccines and therapeutic agents. This study aimed to investigate the immunogenicity of an aluminum hydroxide (Alum) and CpG adjuvanted inactivated vaccine (IAV) candidate against SARS-CoV-2 in mice. A comparison was made between the immune response of mice vaccinated with the Alum+CpG adjuvant IAV and those vaccinated with the Alum adjuvant IAV. Mice immunized with Alum+CpG adjuvant IAV demonstrated high antibody titers and a durable humoral immune response, as well as a Th1-type cellular immune response. Notably, compared to Alum alone vaccine, the Alum+CpG adjuvant IAV induced significantly higher proportions of GC B cells in the splenocytes of immunized mice. Importantly, the changes in inflammatory cytokine levels in the sera of mice vaccinated with the Alum+CpG adjuvant IAV followed a similar trend to that of the Alum adjuvant IAV, which had been proven safe in clinical trials. Overall, our results demonstrate that Alum+CpG adjuvant has the potential to serve as a novel adjuvant, thereby providing valuable insights into the development of vaccine formulations.
Topics: Animals; Mice; Aluminum Hydroxide; COVID-19; SARS-CoV-2; Adjuvants, Immunologic
PubMed: 37640568
DOI: 10.1016/j.vaccine.2023.08.061 -
Journal of Inorganic Biochemistry Mar 2020The use of vaccines containing aluminum (Al) adjuvants is widespread in ovine production. Al adjuvants induce an effective immune-response but lead to the formation of...
The use of vaccines containing aluminum (Al) adjuvants is widespread in ovine production. Al adjuvants induce an effective immune-response but lead to the formation of post-vaccination granulomas from which Al can disseminate. This work aims to study the accumulation of Al in the central nervous system of sheep subcutaneously inoculated with Al-hydroxide containing products. Lumbar spinal cord and parietal lobe from 21 animals inoculated with 19 doses of Vaccine (n = 7), Adjuvant-only (n = 7) or phosphate-buffered saline as Control (n = 7) were analyzed with transversely heated graphite furnace atomic absorption spectroscopy and lumogallion staining for Al analytical measurements and Al tisular localization respectively. In the lumbar spinal cord, Al median content was higher in both the Adjuvant-only and Vaccine group (p = .001) compared with the Control group. Animals of the Adjuvant-only group showed the higher individual measurements in the lumbar spinal cord (14.36 μg/g and 7.83 μg/g). In the parietal lobe, Al median content tended to be higher in the Adjuvant-only group compared with Control group (p = .074). Except for three replicates of the Adjuvant-only group, Al content was always below 1 μg/g. In the lumbar spinal cord, lumogallion-reactive Al deposits were more abundant in the gray matter than in the white matter in both Vaccine (p = .034) and Adjuvant-only groups (p = .017) and Al deposits were mostly associated with glial-like cells (p = .042). In the parietal lobe, few Al deposits, which were sometimes related to blood vessels, were found. In sheep, Al-hydroxide adjuvants inoculated in the subcutaneous tissue selectively accumulate in the lumbar spinal cord.
Topics: Adjuvants, Immunologic; Aluminum; Aluminum Hydroxide; Animals; Injections, Subcutaneous; Male; Parietal Lobe; Sheep; Spinal Cord; Tissue Distribution; Vaccines
PubMed: 31901536
DOI: 10.1016/j.jinorgbio.2019.110871 -
Magnetic Resonance in Chemistry : MRC Feb 2021Suspensions of solid particles find applications in many areas-mining, waste treatment, and in pharmaceutical formulations. Pharmaceutical suspensions include...
Suspensions of solid particles find applications in many areas-mining, waste treatment, and in pharmaceutical formulations. Pharmaceutical suspensions include aluminum-adjuvanted vaccines are widely administered to millions of people worldwide annually. Hence, the stability parameters of such suspensions, for example, sedimentation rate and the compactness of the formed sediments, are of great interest to achieve the most optimal and stable formulations. Unlike currently used analytical techniques involving visual observations and/or monitoring of several optical properties using specialized glassware, water proton nuclear magnetic resonance (wNMR) used in this work allows one to analyze samples in their original sealed container regardless of its opacity and/or labeling. It was demonstrated that the water proton transverse relaxation rate could be used to monitor in real time the sedimentation process of two widely used aluminum adjuvants-Alhydrogel® and Adju-Phos®. Using wNMR, we obtained valuable information on the sedimentation rate, dynamics of the supernatant and sediment formation, and the sedimentation volume ratio (SVR) reflecting the compactness of the formed sediment. Results on SVR from wNMR were verified by caliper measurements. Verification of the sedimentation rate results from wNMR by other analytical techniques is challenging due to differences in the measured attributes and even units of the reported rate. Nonetheless, our results demonstrate the practical applicability of wNMR as an analytical tool to study pharmaceutical suspensions, for example, aluminum-adjuvanted vaccines, to provide higher quality and more efficient vaccines. Such analyses could be carried out in the original container of a suspension drug product to study its colloidal stability and to monitor its quality over time without compromising product integrity.
Topics: Adjuvants, Immunologic; Aluminum Compounds; Aluminum Hydroxide; Kinetics; Phosphates; Physical Phenomena; Proton Magnetic Resonance Spectroscopy; Water
PubMed: 32888244
DOI: 10.1002/mrc.5096 -
Annales Pharmaceutiques Francaises Jul 2017We reviewed the three reference toxicokinetic studies commonly used to suggest innocuity of aluminum (Al)-based adjuvants. A single experimental study was carried out... (Review)
Review
We reviewed the three reference toxicokinetic studies commonly used to suggest innocuity of aluminum (Al)-based adjuvants. A single experimental study was carried out using isotopic Al (Flarend et al., 1997). This study ignored adjuvant cell capture. It was conducted over a short period of time (28 days) and used only two rabbits per adjuvant. At the endpoint, Al retention was 78% for aluminum phosphate and 94% for aluminum hydroxide, both results being incompatible with quick elimination of vaccine-derived Al in urines. Tissue distribution analysis omitted three important retention sites: the injected muscle, the draining lymph node and bone. Two theoretical studies have evaluated the potential risk of vaccine Al in infants, by reference to the oral Minimal Risk Level (MRL) extrapolated from animal studies. Keith et al., 2002 used a too high MRL (2mg/kg/d), an erroneous model of 100% immediate absorption of vaccine Al, and did not consider renal and blood-brain barrier immaturity. Mitkus et al. (2011) only considered absorbed Al, with erroneous calculations of absorption duration. They ignored particulate Al captured by immune cells, which play a role in systemic diffusion and the neuro-inflammatory potential of the adjuvant. MRL they used was both inappropriate (oral Al vs injected adjuvant) and far too high (1mg/kg/d) with regard to experimental studies of Al-induced memory and behavioral changes. Both paucity and serious weaknesses of these studies strongly suggest that novel experimental studies of Al adjuvants toxicokinetics should be performed on the long-term, including post-natal and adult exposures, to ensure innocuity and restore population confidence in Al-containing vaccines.
Topics: Adjuvants, Immunologic; Aluminum; Aluminum Compounds; Aluminum Hydroxide; Animals; Humans; Phosphates; Rabbits; Reference Values; Tissue Distribution; Toxicokinetics; Vaccines
PubMed: 28576261
DOI: 10.1016/j.pharma.2017.04.004 -
Chemical Society Reviews Nov 2014Concern over the economics of accessing fossil fuel reserves, and widespread acceptance of the anthropogenic origin of rising CO2 emissions and associated climate change... (Review)
Review
Concern over the economics of accessing fossil fuel reserves, and widespread acceptance of the anthropogenic origin of rising CO2 emissions and associated climate change from combusting such carbon sources, is driving academic and commercial research into new routes to sustainable fuels to meet the demands of a rapidly rising global population. Here we discuss catalytic esterification and transesterification solutions to the clean synthesis of biodiesel, the most readily implemented and low cost, alternative source of transportation fuels to meet future societal demands.
Topics: Aluminum Hydroxide; Biofuels; Catalysis; Composite Resins; Esterification; Magnesium Hydroxide; Metals, Alkali; Metals, Alkaline Earth; Oxides; Silicon Dioxide; Transition Elements
PubMed: 24957179
DOI: 10.1039/c4cs00189c -
American Journal of Health-system... May 2017Beyond-use dating (BUD) of lidocaine alone and in two "magic mouthwash" preparations stored in amber oral syringes at room temperature was determined.
PURPOSE
Beyond-use dating (BUD) of lidocaine alone and in two "magic mouthwash" preparations stored in amber oral syringes at room temperature was determined.
METHODS
Two formulations of mouthwash containing oral topical lidocaine 2% (viscous), diphenhydramine 2.5 mg/mL, and aluminum hydroxide-magnesium hydroxide-simethicone were prepared in 1:1:1 and 1:2.5:2.5 ratios, divided into 3-mL samples, and stored in unit-dose oral amber syringes. Unit-dose single-product lidocaine samples were also prepared to serve as controls and stored in oral amber syringes. The lidocaine concentrations in these samples were measured periodically for 90 days. A stability-indicating high-performance liquid chromatographic method was developed and validated for system suitability, accuracy, repeatability, intermediate precision, specificity, linearity, and robustness.
RESULTS
Based on the calculated percentages versus the initial concentration and the results from an analysis of variance comparing the two formulations, a BUD of 21 days is deemed appropriate for both magic mouthwash formulations. Based on the stability data, published safety concerns, and lack of efficacy in combination, packaging and dispensing lidocaine separately from other ingredients are recommended when administering magic mouthwash mixtures. Utilizing a 90-day BUD, lidocaine can be packaged separately from other magic mouthwash ingredients in individual dosage units and applied to the oral cavity using the swish-and-spit method. The delivery of the diphenhydramine and aluminum hydroxide-magnesium hydroxide-simethicone could be separated, allowing for a swish-and-swallow method of administration.
CONCLUSION
A BUD of 21 days is recommended for lidocaine prepared with diphenhydramine and aluminum hydroxide-magnesium hydroxide-simethicone in ratios of 1:1:1 and 1:2.5:2.5 and stored at room temperature in amber oral plastic syringes.
Topics: Administration, Oral; Aluminum Hydroxide; Analgesics; Antineoplastic Agents; Diphenhydramine; Drug Combinations; Drug Compounding; Drug Packaging; Drug Stability; Drug Storage; Humans; Lidocaine; Magnesium Hydroxide; Mouth Mucosa; Mouthwashes; Neoplasms; Simethicone; Stomatitis; Syringes; Temperature
PubMed: 28438825
DOI: 10.2146/ajhp160214 -
Biomaterials Jun 2018Aluminum salt (Alum) is one of the most important immune adjuvants approved for use in humans, however it is not suitable for vaccination against various chronic...
Aluminum salt (Alum) is one of the most important immune adjuvants approved for use in humans, however it is not suitable for vaccination against various chronic infectious diseases and cancers for not being able to induce cell-mediated (Th1) immunity. Here, we encapsulated an Alum colloid inside β-glucan particles (GPs), which are a type of natural particles derived from the yeast glucan shells, to prepare hybrid GP-Alum (GP-Al) adjuvant particles with a very uniform size of 2-4 μm. These hybrid particles can be used to load antigen proteins through a simple mixing procedure, and can be highly specifically targeted to antigen-presenting cells (APCs) and strongly activate dendritic cells (DCs) maturation and cytokine secretion. In an animal model, they elicit a strong Th1-biased immune response and extremely high antibody titer, and cause marked prophylactic and therapeutic effects against tumors. As Alum has been proven to be a safe adjuvant to induce strong humoral responses and β-glucans are safe for human use, this very uniform hybrid Alum particulate system could have important application as a vaccine carrier to stimulate humoral and cellular immune responses at the same time.
Topics: Adjuvants, Immunologic; Aluminum Hydroxide; Animals; Cancer Vaccines; Cells, Cultured; Drug Carriers; Glucans; Humans; Immunity, Cellular; Immunity, Humoral; Mice, Inbred C57BL; Saccharomyces cerevisiae
PubMed: 29554479
DOI: 10.1016/j.biomaterials.2018.03.014 -
Journal of Pharmaceutical Sciences Feb 2024Aluminum hydroxide adjuvants are widely used in human vaccines, such as diphtheria, tetanus, hepatitis A and hepatitis B vaccines. The adsorption of antigens on aluminum...
Aluminum hydroxide adjuvants are widely used in human vaccines, such as diphtheria, tetanus, hepatitis A and hepatitis B vaccines. The adsorption of antigens on aluminum hydroxide adjuvants determines the immune boosting effect of vaccines, but it is not clear how changes in physicochemical properties resulting from the production and formulation processes affect the adsorption of aluminum hydroxide adjuvants with antigens. In this study, the commercial aluminum hydroxide adjuvant Alhydrogel® was pretreated by commonly used processes such as autoclaving and calcination, and the changes of aluminum hydroxide adjuvant in physicochemical properties during the treatment were then comprehensively characterized. The adsorption of ovalbumin (OVA) with treated Alhydrogel®, was also investigated, it was found that the decrease in specific surface area caused by the autoclaving process reduced the adsorptive capacity of the antigen, and the adsorptive strength of antigen was decreased only when the surface hydroxyl groups and chemically bound water of adjuvant were reduced by calcination. These findings help to optimize the production and formulation process of adjuvants for the rational regulation of antigen adsorption in vaccines.
Topics: Humans; Aluminum Hydroxide; Aluminum; Adsorption; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Hepatitis B Vaccines
PubMed: 37813301
DOI: 10.1016/j.xphs.2023.10.009