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Children with Kawasaki disease are prescribed acetylsalicylic acid powder as an antipyretic analgesic and antiplatelet agent; however, some of it remains in the mouth, leading to a bitter or sour taste. To address this issue, an in-hospital mini-tablet formulation of acetylsalicylic acid was developed. In order to use the mini-tablets safely and effectively, dissolution tests alone are not sufficient. Therefore, an open-label crossover study on six healthy participants was conducted to evaluate comparative pharmacokinetic parameters. The pharmacokinetic parameters of salicylic acid were Cmax: 4.80 ± 0.79 mg/L (powder; P), 5.03 ± 0.97 mg/L (mini-tablet; MT), AUC0–12: 18.0 ± 3.03 mg-h/L (P), 18.9 ± 4.59 mg-h/L (MT), those of acetylsalicylic acid Cmax: 0.50 ± 0.20 mg/L (P), 0.41 ± 0.24 mg/L (MT), AUC0–12: 0.71 ± 0.27 mg-h/L (P), 0.61 ± 0.36 mg-h/L (MT), with no significant differences between the mini-tablet and powder formulations. Although pharmacokinetic results obtained from adults cannot be directly applied to children, the results of this study are important for predicting pharmacokinetics. Furthermore, a formulation that can improve medication adherence in children who have difficulty taking acetylsalicylic acid powder, thus contributing to pediatric drug therapy. [ABSTRACT FROM AUTHOR]

Children with Kawasaki disease are prescribed acetylsalicylic acid powder as an antipyretic analgesic and antiplatelet agent; however, some of it remains in the mouth, leading to a bitter or sour taste. To address this issue, an in-hospital mini-tablet formulation of acetylsalicylic acid was developed. In order to use the mini-tablets safely and effectively, dissolution tests alone are not sufficient. Therefore, an open-label crossover study on six healthy participants was conducted to evaluate comparative pharmacokinetic parameters. The pharmacokinetic parameters of salicylic acid were Cmax: 4.80 ± 0.79 mg/L (powder; P), 5.03 ± 0.97 mg/L (mini-tablet; MT), AUC0–12: 18.0 ± 3.03 mg-h/L (P), 18.9 ± 4.59 mg-h/L (MT), those of acetylsalicylic acid Cmax: 0.50 ± 0.20 mg/L (P), 0.41 ± 0.24 mg/L (MT), AUC0–12: 0.71 ± 0.27 mg-h/L (P), 0.61 ± 0.36 mg-h/L (MT), with no significant differences between the mini-tablet and powder formulations. Although pharmacokinetic results obtained from adults cannot be directly applied to children, the results of this study are important for predicting pharmacokinetics. Furthermore, a formulation that can improve medication adherence in children who have difficulty taking acetylsalicylic acid powder, thus contributing to pediatric drug therapy.

Bacterial nanocellulose (BNC) is a novel nanomaterial known for its large surface area, biocompatibility, and non-toxicity. BNC contributes to regenerative processes in the skin but lacks antimicrobial and anti-inflammatory properties. Herein, the development of bioactive wound dressings by loading antibacterial povidone-iodine (PVI) or anti-inflammatory acetylsalicylic acid (ASA) into bacterial cellulose is presented. BNC is produced using Hestrin–Schramm culture media and loaded via immersion in PVI and ASA. Through scanning electron microscopy, BNC reveals open porosity where the bioactive compounds are loaded; the mechanical tests show that the dressing prevents mechanical wear. The loading kinetic and release assays (using the Franz cell method) under simulated fluids present a maximum loading of 589.36 mg PVI/g BNC and 38.61 mg ASA/g BNC, and both systems present a slow release profile at 24 h. Through histology, the complete diffusion of the bioactive compounds is observed across the layers of porcine skin. Finally, in the antimicrobial experiment, BNC/PVI produced an inhibition halo for Gram-positive and Gram-negative bacteria, confirming the antibacterial activity. Meanwhile, the protein denaturation test shows effective anti-inflammatory activity in BNC/ASA dressings. Accordingly, BNC is a suitable platform for the development of bioactive wound dressings, particularly those with antibacterial and anti-inflammatory properties. [ABSTRACT FROM AUTHOR]

Alcoholism is one of the most common diseases that can lead to the development of several chronic diseases including steatosis, and cognitive dysfunction. Statins are lipid-lowering drugs that are commonly prescribed for patients with fatty liver diseases; however, the exact effect of statins on cognitive function is still not fully understood. In the present study, we have investigated the molecular and microscopic basis of cognitive impairment induced by alcohol and/or Atorvastatin (ATOR) administration to male Wistar albino rats and explored the possible protective effect of acetylsalicylic acid (ASA). The biochemical analysis indicated that either alcohol or ATOR or together in combination produced a significant increase in the nucleotide-binding domain–like receptor 3 (NLRP3), interleukin-1β (IL-1β) miRNA155 expression levels in the frontal cortex of the brain tissue. The histological and morphometric analysis showed signs of degeneration in the neurons and the glial cells with aggregations of inflammatory cells and a decrease in the mean thickness of the frontal cortex. Immunohistochemical analysis showed a significant increase in the caspase-8 immunoreaction in the neurons and glial cells of the frontal cortex. Interestingly, administration of ASA reversed the deleterious effect of the alcohol and ATOR intake and improved the cognitive function as indicated by biochemical and histological analysis. ASA significantly decreased the expression levels of miRNA155, NLRP3, and IL1B, and produced a significant decrease in caspase-8 immunoreaction in the neurons and glial cells of the frontal cortex with a reduction in the process of neuroinflammation and neuronal damage. To further investigate these findings, we have performed an extensive molecular docking study to investigate the binding affinity of ASA to the binding pockets of the NLRP3 protein. Our results indicated that ASA has high binding scores toward the active sites of the NLRP3 NACHT domain with the ability to bind to the NLRP3 pockets by a set of hydrophilic and hydrophobic interactions. Taken together, the present study highlights the protective pharmacological effect of ASA to attenuate the deleterious effect of alcohol intake and long term ATOR therapy on the cognitive function via targeting miRNA155 and NLRP3 proteins. [ABSTRACT FROM AUTHOR]

Bacterial nanocellulose (BNC) is a novel nanomaterial known for its large surface area, biocompatibility, and non-toxicity. BNC contributes to regenerative processes in the skin but lacks antimicrobial and anti-inflammatory properties. Herein, the development of bioactive wound dressings by loading antibacterial povidone-iodine (PVI) or anti-inflammatory acetylsalicylic acid (ASA) into bacterial cellulose is presented. BNC is produced using Hestrin–Schramm culture media and loaded via immersion in PVI and ASA. Through scanning electron microscopy, BNC reveals open porosity where the bioactive compounds are loaded; the mechanical tests show that the dressing prevents mechanical wear. The loading kinetic and release assays (using the Franz cell method) under simulated fluids present a maximum loading of 589.36 mg PVI/g BNC and 38.61 mg ASA/g BNC, and both systems present a slow release profile at 24 h. Through histology, the complete diffusion of the bioactive compounds is observed across the layers of porcine skin. Finally, in the antimicrobial experiment, BNC/PVI produced an inhibition halo for Gram-positive and Gram-negative bacteria, confirming the antibacterial activity. Meanwhile, the protein denaturation test shows effective anti-inflammatory activity in BNC/ASA dressings. Accordingly, BNC is a suitable platform for the development of bioactive wound dressings, particularly those with antibacterial and anti-inflammatory properties.

Alcoholism is one of the most common diseases that can lead to the development of several chronic diseases including steatosis, and cognitive dysfunction. Statins are lipid-lowering drugs that are commonly prescribed for patients with fatty liver diseases; however, the exact effect of statins on cognitive function is still not fully understood. In the present study, we have investigated the molecular and microscopic basis of cognitive impairment induced by alcohol and/or Atorvastatin (ATOR) administration to male Wistar albino rats and explored the possible protective effect of acetylsalicylic acid (ASA). The biochemical analysis indicated that either alcohol or ATOR or together in combination produced a significant increase in the nucleotide-binding domain–like receptor 3 (NLRP3), interleukin-1β (IL-1β) miRNA155 expression levels in the frontal cortex of the brain tissue. The histological and morphometric analysis showed signs of degeneration in the neurons and the glial cells with aggregations of inflammatory cells and a decrease in the mean thickness of the frontal cortex. Immunohistochemical analysis showed a significant increase in the caspase-8 immunoreaction in the neurons and glial cells of the frontal cortex. Interestingly, administration of ASA reversed the deleterious effect of the alcohol and ATOR intake and improved the cognitive function as indicated by biochemical and histological analysis. ASA significantly decreased the expression levels of miRNA155, NLRP3, and IL1B, and produced a significant decrease in caspase-8 immunoreaction in the neurons and glial cells of the frontal cortex with a reduction in the process of neuroinflammation and neuronal damage. To further investigate these findings, we have performed an extensive molecular docking study to investigate the binding affinity of ASA to the binding pockets of the NLRP3 protein. Our results indicated that ASA has high binding scores toward the active sites of the NLRP3 NACHT domain with the ability to bind to the NLRP3 pockets by a set of hydrophilic and hydrophobic interactions. Taken together, the present study highlights the protective pharmacological effect of ASA to attenuate the deleterious effect of alcohol intake and long term ATOR therapy on the cognitive function via targeting miRNA155 and NLRP3 proteins.

Polymeric implants loaded with drugs can overcome the disadvantages of oral or injection drug administration and deliver the drug locally. Several methods can load drugs into polymers. Herein, soaking and supercritical CO2 (scCO2) impregnation methods were employed to load aspirin into poly(l-lactic acid) (PLLA) and linear low-density polyethylene (LLDPE). Higher drug loadings (DL) were achieved with scCO2 impregnation compared to soaking and in a shorter time (3.4 ± 0.8 vs. 1.3 ± 0.4% for PLLA; and 0.4 ± 0.5 vs. 0.6 ± 0.5% for LLDPE), due to the higher swelling capacity of CO2. The higher affinity of aspirin explained the higher DL in PLLA than in LLDPE. Residual solvent was detected in LLDPE prepared by soaking, but within the FDA concentration limits. The solvents used in both methods acted as plasticizers and increased PLLA crystallinity. PLLA impregnated with aspirin exhibited faster hydrolysis in vitro due to the catalytic effect of aspirin. Finally, PLLA impregnated by soaking showed a burst release because of aspirin crystals on the PLLA surface, and released 100% of aspirin within 60 days, whereas the PLLA prepared with scCO2 released 60% after 74 days by diffusion and PLLA erosion. Hence, the scCO2 impregnation method is adequate for higher aspirin loadings and prolonged drug release.

Dissolution and disintegration of solid dosage forms such as multiple-layer tablet with different active ingredients depend on formulation and properties used in the formulations, and it may sometimes result in counterintuitive release kinetics. In this manuscript, we investigate the behavior of combined acetylsalicylic acid and mefenamic acid bi- and triple-layer formulations. We show that the simulation model with a cellular automata predicted the impact of the inert layer between the different active ingredients on each drug release and provide a good agreement with the experimental results. Also, it is shown that the analysis based on the Noyes–Whitney equation in combination with a cellular automata-supported dissolution and disintegration numerical solutions explain the nature of the unexpected effects. We conclude that the proposed simulation approach is valuable to predict the influence of material attributes and process parameters on drug release from multicomponent and multiple-layer pharmaceutical tablets and to help us develop the drug product formulation.

Polymeric implants loaded with drugs can overcome the disadvantages of oral or injection drug administration and deliver the drug locally. Several methods can load drugs into polymers. Herein, soaking and supercritical CO2 (scCO2) impregnation methods were employed to load aspirin into poly(l-lactic acid) (PLLA) and linear low-density polyethylene (LLDPE). Higher drug loadings (DL) were achieved with scCO2 impregnation compared to soaking and in a shorter time (3.4 ± 0.8 vs. 1.3 ± 0.4% for PLLA; and 0.4 ± 0.5 vs. 0.6 ± 0.5% for LLDPE), due to the higher swelling capacity of CO2. The higher affinity of aspirin explained the higher DL in PLLA than in LLDPE. Residual solvent was detected in LLDPE prepared by soaking, but within the FDA concentration limits. The solvents used in both methods acted as plasticizers and increased PLLA crystallinity. PLLA impregnated with aspirin exhibited faster hydrolysis in vitro due to the catalytic effect of aspirin. Finally, PLLA impregnated by soaking showed a burst release because of aspirin crystals on the PLLA surface, and released 100% of aspirin within 60 days, whereas the PLLA prepared with scCO2 released 60% after 74 days by diffusion and PLLA erosion. Hence, the scCO2 impregnation method is adequate for higher aspirin loadings and prolonged drug release. [ABSTRACT FROM AUTHOR]

The present investigation aimed to assess the combinational effect of commonly used antipyretics and antiseptics with ethanolic extracts of propolis (EEPs) on the growth inhibition of Staphylococcus aureus. The broth microdilution checkerboard assay revealed synergistic interactions between all investigated antipyretics, namely acetylsalicylic acid, ibuprofen, and acetaminophen, with EEPs samples. The values of the fractional inhibitory concentration (ΣFIC) index for all these combinations were <0.5. While, in the case of considered antiseptics, namely chlorhexidine, octenidine dihydrochloride, and 2-phenoxyethanol, the positive interaction was confirmed only for the last one (values of ΣFIC in the range 0.0625–0.25). Combinations of two other agents with all four samples of EEPs resulted in an important antagonistic effect (values of ΣFIC ≥ 4.5). Propolis is mostly dedicated to the treatment of skin/wound infections; thus, these findings are of particular practical importance. The outcomes of the study also support the hypothesis that the propolis's antimicrobial effect is due to the combined (synergistic) action of several ingredients rather than the presence of one component of high antibacterial activity. The composition of 13 ingredients of EEPs (at a concentration below the MIC (minimum inhibitory concentration) of the most active agent) exhibited considerably high anti-staphylococcal efficiency with MIC = 128 µg/mL. [ABSTRACT FROM AUTHOR]

Dissolution and disintegration of solid dosage forms such as multiple-layer tablet with different active ingredients depend on formulation and properties used in the formulations, and it may sometimes result in counterintuitive release kinetics. In this manuscript, we investigate the behavior of combined acetylsalicylic acid and mefenamic acid bi- and triple-layer formulations. We show that the simulation model with a cellular automata predicted the impact of the inert layer between the different active ingredients on each drug release and provide a good agreement with the experimental results. Also, it is shown that the analysis based on the Noyes–Whitney equation in combination with a cellular automata-supported dissolution and disintegration numerical solutions explain the nature of the unexpected effects. We conclude that the proposed simulation approach is valuable to predict the influence of material attributes and process parameters on drug release from multicomponent and multiple-layer pharmaceutical tablets and to help us develop the drug product formulation. [ABSTRACT FROM AUTHOR]