Evaluation and imaging of biodistribution of magnetic nanoparticles in a model of hepatic cirrhosis via alternating current biosusceptometry.

In recent years, magnetic nanoparticles (MNPs) have exhibited theragnostic characteristics which confer a wide range of applications in the biomedical field. Consequently, through Alternating Current Biosusceptometry (ACB), magnetic nanoparticles can be used as tracers, allowing the study of healthy and cirrhotic livers and providing the ability to differentiate them through the reconstruction of quantitative images. The ACB system consists of a developing biomagnetic technique that has the ability to magnetize and measure the magnetic susceptibility of a material such as MNPs, thereby offering quantitative information about biological systems with magnetic tracers.

Non-invasive biomagnetic assessment of gastrointestinal motility in a loperamide-induced constipation model

Constipation is a disorder of the gastrointestinal (GI) and some of the main etiological mechanisms are directly related to changes in GI physiology. The capacity to carry out paired assessments and measure GI parameters under the influence of constipation is a relevant point in selecting a suitable methodology. We aimed to perform a non-invasive investigation of gastrointestinal motility in constipated rats using the alternating current biosusceptometry system (ACB). The animals were split into two groups: the pre-induction stage (CONTROL) and post-induction loperamide stage (LOP). We assessed GI motility parameters using the ACB system. Colon morphometric and immunohistochemical analyses were performed for biomarkers (C-kit) for interstitial cells of Cajal (ICC). Our results showed a significant increase in gastrointestinal transit in the LOP group in addition to a reduction in the dominant frequency of gastric contraction and an arrhythmic profile. A change in colonic contractility profiles was observed, indicating colonic dysmotility in the LOP group. We found a reduction in the number of biomarkers for intestinal cells of Cajal (ICC) in the LOP group. The ACB system can evaluate transit irregularities and their degrees of severity, while also supporting research into novel, safer, and more efficient treatments for constipation.

Quantitative imaging of magnetic nanoparticles in an unshielded environment using a large AC susceptibility array.

BACKGROUND: Non-invasive magnetic imaging techniques are necessary to assist magnetic nanoparticles in biomedical applications, mainly detecting their distribution inside the body. In Alternating Current Biosusceptometry (ACB), the magnetic nanoparticle's magnetization response under an oscillating magnetic field, which is applied through an excitation coil, is detected with a balanced detection coil system. RESULTS: We built a Multi-Channel ACB system (MC-ACB) containing nineteen pick-up coils and obtained 2D quantitative images of magnetic nanoparticle distributions by solving an inverse problem. We reconstructed the magnetic nanoparticles spatial distributions in a field of view of 14 × 14 cm2 with a spatial resolution of 2.0 cm and sensitivity in the milligram scale. A correlation coefficient between quantitative reconstructed and nominal magnetic nanoparticle distributions above 0.6 was found for all measurements. CONCLUSION: Besides other interesting features such as sufficient large field of view dimension for mice and rat studies, portability, and the ability to assess the quantitative magnetic nanoparticles distributions in real-time, the MC-ACB system is a promising tool for quantitative imaging of magnetic nanoparticles distributions in real-time, offering an affordable setup for easy access in clinical or laboratory environments.

Biodistribution Profile of Magnetic Nanoparticles in Cirrhosis-Associated Hepatocarcinogenesis in Rats by AC Biosusceptometry.

Since magnetic nanoparticles (MNPs) have been used as multifunctional probes to diagnose and treat liver diseases in recent years, this study aimed to assess how the condition of cirrhosis-associated hepatocarcinogenesis alters the biodistribution of hepatic MNPs. Using a real-time image acquisition approach, the distribution profile of MNPs after intravenous administration was monitored using an AC biosusceptometry (ACB) assay. We assessed the biodistribution profile based on the ACB images obtained through selected regions of interest (ROIs) in the heart and liver position according to the anatomical references previously selected. The signals obtained allowed for the quantification of pharmacokinetic parameters, indicating that the uptake of hepatic MNPs is compromised during liver cirrhosis, since scar tissue reduces blood flow through the liver and slows its processing function. Since liver monocytes/macrophages remained constant during the cirrhotic stage, the increased intrahepatic vascular resistance associated with impaired hepatic sinusoidal circulation was considered the potential reason for the change in the distribution of MNPs.

Long-Term Clearance and Biodistribution of Magnetic Nanoparticles Assessed by AC Biosusceptometry.

Once administered in an organism, the physiological parameters of magnetic nanoparticles (MNPs) must be addressed, as well as their possible interactions and retention and elimination profiles. Alternating current biosusceptometry (ACB) is a biomagnetic detection system used to detect and quantify MNPs. The aims of this study were to evaluate the biodistribution and clearance of MNPs profiles through long-time in vivo analysis and determine the elimination time carried out by the association between the ACB system and MnFe2O4 nanoparticles. The liver, lung, spleen, kidneys, and heart and a blood sample were collected for biodistribution analysis and, for elimination analysis, and over 60 days. During the period analyzed, the animal's feces were also collectedd. It was possible to notice a higher uptake by the liver and the spleen due to their characteristics of retention and uptake. In 60 days, we observed an absence of MNPs in the spleen and a significant decay in the liver. We also determined the MNPs' half-life through the liver and the spleen elimination. The data indicated a concentration decay profile over the 60 days, which suggests that, in addition to elimination via feces, there is an endogenous mechanism of metabolization or possible agglomeration of MNPs, resulting in loss of ACB signal intensity.

The Influence of Omeprazole on the Dissolution Processes of pH-Dependent Magnetic Tablets Assessed by Pharmacomagnetography.

Pharmacomagnetography involves the simultaneous assessment of solid dosage forms (SDFs) in the human gastrointestinal (GI) tract and the drug plasmatic concentration, using a biomagnetic technique and pharmacokinetics analysis. This multi-instrumental approach helps the evaluation, as GI variables can interfere with the drug delivery processes. This study aimed to employ pharmacomagnetography to evaluate the influence of omeprazole on the drug release and absorption of metronidazole administered orally in magnetic-coated tablets. Magnetic-coated tablets, coated with Eudragit® E-100 (E100) and containing 100 mg of metronidazole, were produced. For the in vivo experiments, 12 volunteers participated in the two phases of the study (placebo and omeprazole) on different days to assess the bioavailability of metronidazole. The results indicated a shift as the pH of the solution increased and a delay in the dissolution of metronidazole, showing that the pH increase interferes with the release processes of tablets coated with E100. Our study reinforced the advantages of pharmacomagnetography as a tool to perform a multi-instrumental correlation analysis of the disintegration process and the bioavailability of drugs.

An easy and low-cost biomagnetic methodology to study regional gastrointestinal transit in rats.

The identification of gastrointestinal (GI) motility disorders requires the evaluation of regional GI transit, and the development of alternative methodologies in animals has a significant impact on translational approaches. Therefore, the purpose of this study was to validate an easy and low-cost methodology (alternate current biosusceptometry - ACB) for the assessment of regional GI transit in rats through images. Rats were fed a test meal containing magnetic tracer and phenol red, and GI segments (stomach, proximal, medial and distal small intestine, and cecum) were collected to assess tracer's retention at distinct times after ingestion (0, 60, 120, 240, and 360 min). Images were obtained by scanning the segments, and phenol red concentration was determined by the sample's absorbance. The temporal retention profile, geometric center, gastric emptying, and cecum arrival were evaluated. The correlation coefficient between methods was 0.802, and the temporal retention of each segment was successfully assessed. GI parameters yielded comparable results between methods, and ACB images presented advantages as the possibility to visualize intrasegmental tracer distribution and the automated scan of the segments. The imaging approach provided a reliable assessment of several parameters simultaneously and may serve as an accurate and sensitive approach for regional GI research in rats.