Biocompatible N-acetyl-nanoconstruct alleviates lipopolysaccharide-induced acute lung injury in vivo

Kim

et al. 2022

ACS Appl. Nano Mater.

Self Cite

As injected drugs finally diffuse to the target cells, a quantitative understanding of the diffusion behavior of drug molecules or drug carriers is essential for the determination of their efficacy or optimal doses. Here, we propose a method for determining the diffusivity (D, diffusion coefficient) of drug carriers in tissue-mimicking collagen in the lab-on-a-chip (LOC) platform and predict their spatiotemporal distribution using the calculated D. By controlling the concentrations of fluorescent mesoporous silica nanoparticles (MSNs) in each channel, the diffusion of fluorescent MSNs was induced and fluorescence gradients in collagen were produced and captured as images. The D of the MSNs by size was obtained by fitting the fluorescence profiles to the solution of Fick’s second law. The D of MSNs varied by size from 2.98 × 10–10 m2/s (MSNs of 10 nm) to 1.14 × 10–11 m2/s (MSNs of 1 μm). The spatiotemporal profiles of MSNs were calculated using the obtained D, and it was demonstrated that the concentration of MSNs with a size >200 nm at 100 μm from the gel–liquid interface will remain <50% of that in the vessel-mimicking channel even after 3 h. As the analysis and prediction procedures based on fluorescence profile image processing and a least-squares fit to the solution are relatively simple, our results can be extended to various studies to narrow the gap between in vitro tests and animal experiments in drug or particle transport research through the calculation of the diffusion coefficient of drug candidates before animal experiments and might replace some parts of animal experiments of drug delivery studies.

Section: Resultsmentioning

confidence: 99%

“…MSNs were prepared according to a previously reported sol–gel method with modification. , CTAB with TMOS or TEOS was used as a control for pH conditions for an appropriate catalytic reaction. For 10 nm particles, CTAB (83.8 mg) and TMOS (0.096 mL) were reacted in an ammonium hydroxide/ethanol solution at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Spatiotemporal Distribution of Mesoporous Silica Nanoparticles in Tissue-Mimicking Collagen Using Lab-on-a-Chip Technology for Drug Carrier Diffusivity Evaluation

Kim

et al. 2022

ACS Appl. Nano Mater.

Self Cite

“…A study on a mechanically ventilated rat with lipopolysaccharide-induced ALI reported that a high dose of NAC reduced oxidative damage and inflammatory cell in the histology of the lungs [14]. Other studies also reported that NAC treatment protected against lipopolysaccharide-induced ALI [16].…”

Section: Discussionmentioning

confidence: 99%

The Role of Antioxidant Agent (N-Acetylcysteine) in Oleic Acid-Induced Acute Lung Injury in a Rat Model

Kumar¹,

Bhagat²,

Pandey³

et al. 2022

Cureus

ContextReactive oxygen species (ROS) produced by inflammatory cells play a major role in mediating lung injury in sepsis or hyperoxic lung injury. AimsN-Acetylcysteine (NAC), an antioxidant, was examined in this research to see whether it helps prevent acute lung injury (ALI). Materials and methodsExperiments were performed on Charles-Foster strain healthy male adult albino rats. All the animals were randomly divided into one control and two experimental groups. In control/group I, saline was administered, and cardiorespiratory parameters were recorded. Oleic acid (OA) was administered in group II to produce ALI. In group III, OA was administered to NAC-pretreated rats, and cardiorespiratory parameters were recorded to observe the effect of NAC on ALI. This study used analysis of variance (ANOVA) with two factors and a post hoc test (multiple comparisons -least significant difference (LSD) test) for statical analysis. For determining survival time, the Mantel-Cox test and Kaplan-Meier survival curves were used. A P value < 0.05 was considered significant. ResultsRespiratory arrest, pulmonary edema, and reduced partial pressure of oxygen (PaO 2 )/fraction of inspired oxygen (FiO 2 ) ratio were all indications of OA-induced ALI in rats. The animals in the NAC + OA group had better respiratory and cardiac statistics than those in the OA alone group, and their survival duration was extended. However, NAC pretreatment could not protect the animals against the development of pulmonary edema. ConclusionsThese observations indicate that NAC (an antioxidant agent) protected rats against ALI in the initial phase and prolonged the survival time but failed to prevent the development of pulmonary edema.

“…In addition to reducing NF-κB activity and associated proinflammatory cytokines, these particles also increased antiinflammatory cytokine interleukin-10 (IL-10) (Vuong et al, 2017). Other anti-inflammatory and antioxidant polymers that have demonstrated protection from LPS include N-acetylcysteine gels (Kim et al, 2021), graphene oxide-polypropylene nanoparticles (Fonticoli et al, 2023), and polyphenol gels (Luque et al, 2023), the latter two of which also have antibacterial benefits. In a cecalpuncture and ligation sepsis mouse model, dendrimers scavenged pro-inflammatory cytokines, resulting in a significantly improved survival rate of 100% (Shi et al, 2020).…”

Section: Synthetic Biomaterials For Inflammationmentioning

confidence: 99%

Biomaterials for treating sepsis-induced thromboinflammation

Lutz,

Brown

2023

Front. Biomater. Sci.

Sepsis is a common and life-threatening disorder with an alarmingly high mortality rate. Unfortunately, this rate has not decreased significantly over the last decade and the number of septic cases is increasing each year. Despite sepsis affecting millions of people annually, there is still not an established standard of care. The development of a therapy that targets the thromboinflammation characteristic of sepsis is imperative. Until recently, research has focused on uncovering individual pathways to target. As more of the pathophysiology of sepsis has become understood and more biomarkers uncovered, the interplay between endothelial cells, platelets, and leukocytes has emerged as a critical event. Therefore, a multi-targeted approach is clearly required for designing an effective treatment for sepsis. The versatility of biomaterials offers a promising solution in that they can be designed to target and affect multiple pathways and systems and safely inhibit excessive inflammation while maintaining hemostasis. Already, studies have demonstrated the ability of biomaterials to target different processes and stages in sepsis-induced inflammation and coagulopathy. Moreover, some biomaterials offer inherent anti-inflammatory and hemostatic qualities. This review aims to discuss the most recent advancements in biomaterial development designed to address inflammation, coagulopathy, and thromboinflammation.