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International Journal of Nanomedicine 2015Hydrotalcite-like compounds are two-dimensional inorganic nanolayers also known as clay minerals or anionic clays or layered double hydroxides/layered hydroxy salts, and... (Review)
Review
Hydrotalcite-like compounds are two-dimensional inorganic nanolayers also known as clay minerals or anionic clays or layered double hydroxides/layered hydroxy salts, and have emerged as a single type of material with numerous biomedical applications, such as drug delivery, gene delivery, cosmetics, and biosensing. Inorganic nanolayers are promising materials due to their fascinating properties, such as ease of preparation, ability to intercalate different type of anions (inorganic, organic, biomolecules, and even genes), high thermal stability, delivery of intercalated anions in a sustained manner, high biocompatibility, and easy biodegradation. Inorganic nanolayers have been the focus for researchers over the last decade, resulting in widening application horizons, especially in the field of biomedical science. These nanolayers have been widely applied in drug and gene delivery. They have also been applied in biosensing technology, and most recently in bioimaging science. The suitability of inorganic nanolayers for application in drug delivery, gene delivery, biosensing technology, and bioimaging science makes them ideal materials to be applied for theranostic purposes. In this paper, we review the structure, methods of preparation, and latest advances made by inorganic nanolayers in such biomedical applications as drug delivery, gene delivery, biosensing, and bioimaging.
Topics: Aluminum Hydroxide; Aluminum Silicates; Anti-Infective Agents; Antineoplastic Agents; Antitubercular Agents; Biocompatible Materials; Biosensing Techniques; Clay; Drug Delivery Systems; Gene Transfer Techniques; Hydroxides; Intercalating Agents; Magnesium Hydroxide; Nanostructures
PubMed: 26366081
DOI: 10.2147/IJN.S72330 -
Journal of Pharmaceutical Sciences Jan 2020Subunit vaccines often contain colloidal aluminum salt-based adjuvants to activate the innate immune system. These aluminum salts consist of micrometer-sized aggregates.... (Comparative Study)
Comparative Study
Subunit vaccines often contain colloidal aluminum salt-based adjuvants to activate the innate immune system. These aluminum salts consist of micrometer-sized aggregates. It is well-known that particle size affects the adjuvant effect of particulate adjuvants. In this study, the activation of human monocytes by hexagonal-shaped gibbsite (ø = 210 ± 40 nm) and rod-shaped boehmite (ø = 83 ± 827 nm) was compared with classical aluminum oxyhydroxide adjuvant (alum). To this end, human primary monocytes were cultured in the presence of alum, gibbsite, or boehmite. The transcriptome and proteome of the monocytes were investigated by using quantitative polymerase chain reaction and mass spectrometry. Human monocytic THP-1 cells were used to investigate the effect of the particles on cellular maturation, differentiation, activation, and cytokine secretion, as measured by flow cytometry and enzyme-linked immunosorbent assay. Each particle type resulted in a specific gene expression profile. IL-1ß and IL-6 secretion was significantly upregulated by boehmite and alum. Of the 7 surface markers investigated, only CD80 was significantly upregulated by alum and none by gibbsite or boehmite. Gibbsite hardly activated the monocytes. Boehmite activated human primary monocytes equally to alum, but induced a much milder stress-related response. Therefore, boehmite was identified as a promising adjuvant candidate.
Topics: Adjuvants, Immunologic; Aluminum Hydroxide; Aluminum Oxide; B7-1 Antigen; Cell Differentiation; Colloids; Drug Compounding; Humans; Immunity, Innate; Interleukin-1beta; Interleukin-6; Monocytes; Particle Size; THP-1 Cells; Transcriptome
PubMed: 31449816
DOI: 10.1016/j.xphs.2019.08.014 -
Applied and Environmental Microbiology Feb 1978Adsorption of poliovirus and rotavirus by aluminum hydroxide and activated sludge flocs was studied. Both aluminum hydroxide and activated sludge flocs adsorbed greater... (Comparative Study)
Comparative Study
Adsorption of poliovirus and rotavirus by aluminum hydroxide and activated sludge flocs was studied. Both aluminum hydroxide and activated sludge flocs adsorbed greater amounts of poliovirus than rotavirus. Aluminum hydroxide flocs reduced the titer of poliovirus in tap water by 3 log10, but they only reduced the titer of a simian rotovirus (SA-11) in tap water by 1 log10 or less and did not noticeably reduce the number of human rotavirus particles present in a dilute stool suspension. Activated sludge flocs reduced the titer of added poliovirus by 0.7 to 1.8 log10 and reduced the titer of SA-11 by 0.5 log10 or less. These studies indicate that a basic difference in the adsorptive behavior of enteroviruses and rotaviruses exists and that water and wastewater treatment processes that are highly effective in removal of enteroviruses may not be as effective in removing other viral groups such as rotaviruses.
Topics: Adsorption; Aluminum Hydroxide; Poliovirus; RNA Viruses; Rotavirus; Sewage; Water Microbiology
PubMed: 205173
DOI: 10.1128/aem.35.2.360-363.1978 -
Antimicrobial Agents and Chemotherapy Apr 1992This study was designed to determine the effects of an aluminum hydroxide antacid and a calcium carbonate antacid on the bioavailability of ciprofloxacin (Cipro). Cipro... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
This study was designed to determine the effects of an aluminum hydroxide antacid and a calcium carbonate antacid on the bioavailability of ciprofloxacin (Cipro). Cipro (750 mg) was administered orally to 12 healthy volunteers in a three-way randomized crossover design. The three treatments included Cipro alone, four 850-mg calcium carbonate tablets taken 5 min before Cipro, and three 600-mg aluminum hydroxide tablets taken 5 min before Cipro. The relative bioavailability of Cipro when given with calcium carbonate was approximately 60% of the control value. When Cipro was given with aluminum hydroxide, the relative bioavailability was approximately 15%. Urinary recovery of Cipro in the aluminum hydroxide treatment group was approximately one-fourth of that in the calcium carbonate group. Although calcium carbonate decreased absorption to a lesser extent than aluminum hydroxide, these data suggest that antacids containing either aluminum or calcium should not be given concomitantly with Cipro.
Topics: Adult; Aluminum Hydroxide; Biological Availability; Calcium Carbonate; Ciprofloxacin; Humans; Male
PubMed: 1503446
DOI: 10.1128/AAC.36.4.830 -
Journal of Pharmaceutical Sciences Feb 2015During transport and storage, vaccines may be exposed to temperatures outside of the range recommended for storage, potentially causing efficacy losses. To better...
During transport and storage, vaccines may be exposed to temperatures outside of the range recommended for storage, potentially causing efficacy losses. To better understand and prevent such losses, dominant negative inhibitor (DNI), a recombinant protein antigen for a candidate vaccine against anthrax, was formulated as a liquid and as a glassy lyophilized powder with the adjuvants aluminum hydroxide and glycopyranoside lipid A (GLA). Freeze-thawing of the liquid vaccine caused the adjuvants to aggregate and decreased its immunogenicity in mice. Immunogenicity of liquid vaccines also decreased when stored at 40°C for 8 weeks, as measured by decreases in neutralizing antibody titers in vaccinated mice. Concomitant with efficacy losses at elevated temperatures, changes in DNI structure were detected by fluorescence spectroscopy and increased deamidation was observed by capillary isoelectric focusing (cIEF) after only 1 week of storage of the liquid formulation at 40°C. In contrast, upon lyophilization, no additional deamidation after 4 weeks at 40°C and no detectable changes in DNI structure or reduction in immunogenicity after 16 weeks at 40°C were observed. Vaccines containing aluminum hydroxide and GLA elicited higher immune responses than vaccines adjuvanted with only aluminum hydroxide, with more mice responding to a single dose.
Topics: Adjuvants, Pharmaceutic; Aluminum Hydroxide; Animals; Anthrax Vaccines; Drug Stability; Female; Freeze Drying; Freezing; Glass; Lipid A; Mice; Mice, Inbred BALB C
PubMed: 25581103
DOI: 10.1002/jps.24295 -
Scientific Reports Jul 2021Herpes simplex virus is among the most prevalent sexually transmitted infections. Acyclovir is a potent, selective inhibitor of herpes viruses and it is indicated for...
Herpes simplex virus is among the most prevalent sexually transmitted infections. Acyclovir is a potent, selective inhibitor of herpes viruses and it is indicated for the treatment and management of recurrent cold sores on the lips and face, genital herpes, among other diseases. The problem of the oral bioavailability of acyclovir is limited because of the low permeability across the gastrointestinal membrane. The use of nanoparticles of pseudoboehmite as a drug delivery system in vitro assays is a promising approach to further the permeability of acyclovir release. Here we report the synthesis of high purity pseudoboehmite from aluminium nitrate and ammonium hydroxide containing nanoparticles, using the sol-gel method, as a drug delivery system to improve the systemic bioavailability of acyclovir. The presence of pseudoboehmite nanoparticles were verified by infrared spectroscopy, transmission electron microscopy, and X-ray diffraction techniques. In vivo tests were performed with Wistar rats to compare the release of acyclovir, with and without the addition of pseudoboehmite. The administration of acyclovir with the addition of pseudoboehmite increased the drug content by 4.6 times in the plasma of Wistar rats after 4 h administration. We determined that the toxicity of pseudoboehmite is low up to 10 mg/mL, in gel and the dried pseudoboehmite nanoparticles.
Topics: Acyclovir; Administration, Oral; Aluminum Hydroxide; Aluminum Oxide; Animals; Antiviral Agents; Biological Availability; Caco-2 Cells; Cell Survival; Drug Delivery Systems; Drug Liberation; Herpes Simplex; Humans; Models, Animal; Nanogels; Rats; Rats, Wistar; Simplexvirus
PubMed: 34326377
DOI: 10.1038/s41598-021-94325-y -
JCI Insight Dec 2023IL-12 is a potent cytokine that can promote innate and adaptive anticancer immunity, but its clinical development has been limited by toxicity when delivered...
IL-12 is a potent cytokine that can promote innate and adaptive anticancer immunity, but its clinical development has been limited by toxicity when delivered systemically. Intratumoral (i.t.) administration can expand the therapeutic window of IL-12 and other cytokines but is in turn limited by rapid drug clearance from the tumor, which reduces efficacy, necessitates frequent administration, and increases systemic accumulation. To address these limitations, we developed an anchored IL-12 designated ANK-101, composed of an engineered IL-12 variant that forms a stable complex with the FDA-approved vaccine adjuvant aluminum hydroxide (Alhydrogel). Following i.t. administration of murine ANK-101 (mANK-101) in early intervention syngeneic mouse tumors, the complex formed a depot that was locally retained for weeks as measured by IVIS or SPECT/CT imaging, while unanchored protein injected i.t. was cleared within hours. One or 2 i.t. injections of mANK-101 induced single-agent antitumor activity across a diverse range of syngeneic tumors, including models resistant to checkpoint blockade at doses where unanchored IL-12 had no efficacy. Local treatment with mANK-101 further induced regressions of noninjected lesions, especially when combined with systemic checkpoint blockade. Antitumor activity was associated with remodeling of the tumor microenvironment, including prolonged IFN-γ and chemokine expression, recruitment and activation of T and NK cells, M1 myeloid cell skewing, and increased antigen processing and presentation. Subcutaneous administration of ANK-101 in cynomolgus macaques was well tolerated. Together, these data demonstrate that ANK-101 has an enhanced efficacy and safety profile and warrants future clinical development.
Topics: Mice; Animals; Interleukin-12; Aluminum Hydroxide; Tumor Microenvironment; Cytokines; Neoplasms
PubMed: 38063196
DOI: 10.1172/jci.insight.168224 -
Allergy Mar 2020
Topics: Aluminum Hydroxide; Bee Venoms; Desensitization, Immunologic; Humans; Wasp Venoms
PubMed: 31394011
DOI: 10.1111/all.14012 -
Journal of Immunological Methods Jul 2015The mechanism behind the adjuvant effect of aluminum salts is poorly understood notwithstanding that aluminum salts have been used for decades in clinical vaccines. In...
The mechanism behind the adjuvant effect of aluminum salts is poorly understood notwithstanding that aluminum salts have been used for decades in clinical vaccines. In an aqueous environment and at a nearly neutral pH, the aluminum salts form particulate aggregates, and one plausible explanation of the lack of information regarding the mechanisms could be the absence of an efficient method of tracking phagocytosed aluminum adjuvants and thereby the intracellular location of the adjuvant. In this paper, we want to report upon the use of lumogallion staining enabling the detection of phagocytosed aluminum adjuvants inside viable cells. Including micromolar concentrations of lumogallion in the culture medium resulted in a strong fluorescence signal from cells that had phagocytosed the aluminum adjuvant. The fluorescence appeared as spots in the cytoplasm and by confocal microscopy and co-staining with probes presenting fluorescence in the far-red region of the spectrum, aluminum adjuvants could to a certain extent be identified as localized in acidic vesicles, i.e., lysosomes. Staining and detection of intracellular aluminum adjuvants was achieved not only by diffusion of lumogallion into the cytoplasm, thereby highlighting the presence of the adjuvant, but also by pre-staining the aluminum adjuvant prior to incubation with cells. Pre-staining of aluminum adjuvants resulted in bright fluorescent particulate aggregates that remained fluorescent for weeks and with only a minor reduction of fluorescence upon extensive washing or incubation with cells. Both aluminum oxyhydroxide and aluminum hydroxyphosphate, two of the most commonly used aluminum adjuvants in clinical vaccines, could be pre-stained with lumogallion and were easily tracked intracellularly after incubation with phagocytosing cells. Staining of viable cells using lumogallion will be a useful method in investigations of the mechanisms behind aluminum adjuvants' differentiation of antigen-presenting cells into inflammatory cells. Information will be gained regarding the phagosomal pathways and the events inside the phagosomes, and thereby the ultimate fate of phagocytosed aluminum adjuvants could be resolved.
Topics: Adjuvants, Immunologic; Aluminum Hydroxide; Aluminum Oxide; Animals; Benzenesulfonates; Cell Line, Tumor; Flavonoids; Fluorescent Dyes; Humans; Mice; Mice, Inbred C57BL; Microscopy, Confocal; Phagocytosis; Phosphates; Staining and Labeling
PubMed: 25896212
DOI: 10.1016/j.jim.2015.04.008 -
Molecular Biology Reports Oct 2022A variety of smooth muscle-specific genes and proteins, including SMAD3, BMPR-II, and MRTF, are involved in airway remodeling in asthma. As a receptor of bone...
BACKGROUND
A variety of smooth muscle-specific genes and proteins, including SMAD3, BMPR-II, and MRTF, are involved in airway remodeling in asthma. As a receptor of bone morphogenetic protein (BMP) signaling, BMPR-II has important roles in airway remodeling in asthma. However, the underlying mechanism of BMPR-II in airway smooth muscle cells (ASMCs) in asthma remains incomplete.
METHODS
Wistar rats were intraperitoneally injected with ovalbumin antigen suspension and aluminium hydroxide and, stimulated with ovalbumin nebulized inhalation to constructed asthma model. Primary ASMCs were isolated with collagenase I and identified by testing the α-SMA expression. Quantitative polymerase chain reaction (qPCR) and western blot assay were employed to detect the gene expression. CCK8, Transwell and Fluo-4 A assays were introduced to measure the cell viability, migration and intracellular Ca. Co-Immunoprecipitation (Co-IP) assay was applied to test the interaction among proteins.
RESULTS
First, we observed significant increases in BMPR-II in asthmatic rat model and ASMCs at both the mRNA and protein levels. Second, we observed that silencing of siBMPR-II inhibited proliferation, migratory capacity and intracellular Ca concentration in ASMCs. Furthermore, our study demonstrated that siBMPR-II inhibited the Smad3 expression and overexpression promoted the bioactivity of ASMCs. In addition, this study showed that p-Smad3 could interacted with MRTF and siMRTF inhibits the bioactivity of ASMCs. Finally, our results revealed BMPR-II-SMAD3/MRTF pathway affected the bioactivity of ASMCs.
CONCLUSIONS
This study indicates that the BMPR-II-SMAD3/MRTF signaling pathway is involved in the process of ASMCs remodeling, providing novel avenues for the identification of new therapeutic modalities.
Topics: Airway Remodeling; Aluminum Hydroxide; Animals; Asthma; Bone Morphogenetic Proteins; Cell Proliferation; Collagenases; Myocytes, Smooth Muscle; Ovalbumin; RNA, Messenger; Rats; Rats, Wistar
PubMed: 36008606
DOI: 10.1007/s11033-022-07764-9