The clearance and biodistribution of magnetic composite nanoparticles in healthy and osteoarthritic rat knees.
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ABSTRACT:
SUBMITTER: Partain BD
PROVIDER: S-EPMC7942179 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Increase of subchondral bone area (tAB) in OA has been reported, but it remains unclear if this is specific to OA. We investigated differences in knee tAB after one year in healthy subjects and in those with radiographic OA (rOA).MR images of 899 right knees from the OA Initiative were acquired at baseline and one year follow-up (year-1). Medial and lateral tibial cartilage (MT and LT) and weight-bearing femoral cartilage (cMF and cLF) were segmented and tAB computed. Subjects were stratified into: healthy controls, pre-rOA (K&L grades 0 and 1, with OA risk factors), established rOA (K&L grades 2-4), and independently with regards to joint space narrowing (without, with medial, lateral and bilateral JSN). Primary analysis tested if tAB was different between baseline and year-1 in rOA. Exploratory analyses investigated whether: (1) tAB changes differed between healthy controls and those with rOA; (2) tAB differences were greater in higher K&L grades; and (3) tAB was different between baseline and year-1 in JSN. Significance was set at P < 0.0125.Differences in tAB were found in rOA in MT, cMF and cLF (ranging from +0.2% to +0.4%; P < 0.001), but not in healthy controls or pre-rOA. Rates of change did not differ between groups. Within the JSN groups differences of 0.2-0.4% were found in the femur (P < 0.05).We find that knee tABs differ in rOA between baseline and year-1, but the change was not greater than in healthy knees, and is restricted to the femur in JSN.
| S-EPMC5572564 | biostudies-other
Project description:Nanoparticle (NP) drug delivery systems (5-250 nm) have the potential to improve current disease therapies because of their ability to overcome multiple biological barriers and releasing a therapeutic load in the optimal dosage range. Rapid clearance of circulating nanoparticles during systemic delivery is a critical issue for these systems and has made it necessary to understand the factors affecting particle biodistribution and blood circulation half-life. In this review, we discuss the factors which can influence nanoparticle blood residence time and organ specific accumulation. These factors include interactions with biological barriers and tunable nanoparticle parameters, such as composition, size, core properties, surface modifications (pegylation and surface charge), and finally, targeting ligand functionalization. All these factors have been shown to substantially affect the biodistribution and blood circulation half-life of circulating nanoparticles by reducing the level of nonspecific uptake, delaying opsonization, and increasing the extent of tissue specific accumulation.
| S-EPMC2663893 | biostudies-other
Project description:Understanding intra-articular biodistribution is imperative as candidate osteoarthritis (OA) drugs become increasingly site-specific. Cartilage has been identified as opportunistic for therapeutic intervention, but poses numerous barriers to drug delivery. To facilitate drug delivery to cartilage, nanoscale vehicles have been designed with different features that target the tissue's matrix. However, it is unclear if these targeting strategies are influenced by OA and the associated structural changes that occur in cartilage. The goal of this work was to study the effectiveness of different cartilage-targeting nanomaterials with respect to cartilage localization and retention, and to determine how these outcomes change in OA. To address these questions, a nanoparticle (NP) system was developed, and the formulation was tuned to possess three distinct cartilage-targeting strategies: (1) passive targeting cationic NPs for electrostatic attraction to cartilage, (2) active targeting NPs with binding peptides for collagen type II, and (3) untargeted neutrally-charged NPs. Ex vivo analyses with bovine cartilage explants demonstrated that targeting strategies significantly improved NP associations with both healthy and OA-like cartilage. In vivo studies with collagenase-induced OA in rats revealed that disease state influenced joint biodistribution for all three NP formulations. Importantly, the extent of cartilage accumulation for each NP system was affected by disease differently; with active NPs, but not passive NPs, cartilage accumulation was increased in OA relative to healthy knees. Together, this work suggests that NPs can be strategically designed for site-specific OA drug delivery, but the biodistribution of the NPs are influenced by the disease conditions into which they are delivered. STATEMENT OF SIGNIFICANCE: As emerging drugs for osteoarthritis are becoming increasingly site-specific, the need for targeted intra-articular drug delivery has evolved. To improve drug delivery to cartilage, targeting strategies for nanomaterials have been developed, but the manner in which these targeted systems accumulate at different sites within the joint remains poorly understood. Moreover, it is unclear how nanomaterial-tissue interactions change in osteoarthritic conditions, as tissue structure and composition change after disease onset. By understanding how nanomaterials distribute within healthy and disease joints, we can advance targeted drug delivery strategies and improve therapeutic outcomes for emerging drugs.
| S-EPMC7025912 | biostudies-literature
Project description:Recently, concerns have been raised about potential adverse effects of synthetic amorphous silica, commonly used as food additive (E551), since silica nanoparticles have been detected in food containing E551. We examined the biodistribution and excretion in female Sprague-Dawley rats of NM-200, a well characterized nanostructured silica representative for food applications. A single intravenous injection of NM-200 was applied at a dose of 20 mg/kgbw, followed by autopsy after 6 and 24 h. The main organs where silicon accumulated were liver and spleen. The silicon concentration significantly decreased in spleen between 6 and 24 h. In liver the tendency was the same but the effect was not significant. This could be due to clearance of the spleen to the liver via the splenic vein, while liver clearance takes more time due to hepatic processing and biliary excretion. In treated animals the liver showed in addition a prominent increase of macrophages between both evaluation moments. Within the first 24 h, silicon was mainly excreted through urine. Further studies are necessary to evaluate the toxicokinetics of different types of silica nanomaterials at lower exposure doses in order to be able to predict kinetics and toxicity of silica nanoparticles depending on their physicochemical characteristics.
| S-EPMC6318342 | biostudies-literature
Project description:Knee joint ligaments provide stability to the joint by preventing excessive movement. There has been no systematic effort to study the effect of OA and ageing on the mechanical properties of the four major human knee ligaments. This study aims to collate data on the material properties of the anterior (ACL) and posterior (PCL) cruciate ligaments, medial (MCL) and lateral (LCL) collateral ligaments. Bone-ligament-bone specimens from twelve cadaveric human knee joints were extracted for this study. The cadaveric knee joints were previously collected to study ageing and OA on bone and cartilage material properties; therefore, combining our previous bone and cartilage data with the new ligament data from this study will facilitate subject-specific whole-joint modelling studies. The bone-ligament-bone specimens were tested under tensile loading to failure, determining material parameters including yield and ultimate (failure) stress and strain, secant modulus, tangent modulus, and stiffness. There were significant negative correlations between age and ACL yield stress (p = 0.03), ACL failure stress (p = 0.02), PCL secant (p = 0.02) and tangent (p = 0.02) modulus, and LCL stiffness (p = 0.046). Significant negative correlations were also found between OA grades and ACL yield stress (p = 0.02) and strain (p = 0.03), and LCL failure stress (p = 0.048). However, changes in age or OA grade did not show a statistically significant correlation with the MCL tensile parameters. Due to the small sample size, the combined effect of age and the presence of OA could not be statistically derived. This research is the first to report tensile properties of the four major human knee ligaments from a diverse demographic. When combined with our previous findings on bone and cartilage for the same twelve knee cadavers, the current ligament study supports the conceptualisation of OA as a whole-joint disease that impairs the integrity of many peri-articular tissues within the knee. The subject-specific data pool consisting of the material properties of the four major knee ligaments, subchondral and trabecular bones and articular cartilage will advance knee joint finite element models.
| S-EPMC9446756 | biostudies-literature
Project description:Successful translation of the use of nanoparticles from laboratories to clinics requires exhaustive and elaborate studies involving the biodistribution, clearance, and biocompatibility of nanoparticles for in vivo biomedical applications. We report here the use of multimodal organically modified silica (ORMOSIL) nanoparticles for in vivo bioimaging, biodistribution, clearance, and toxicity studies. We have synthesized ORMOSIL nanoparticles with diameters of 20-25 nm, conjugated with near-infrared (NIR) fluorophores and radiolabeled them with (124)I, for optical and PET imaging in vivo. The biodistribution of the nontargeted nanoparticles was studied in nontumored nude mice by optical fluorescence imaging, as well by measuring the radioactivity from harvested organs. Biodistribution studies showed a greater accumulation of nanoparticles in liver, spleen, and stomach than in kidney, heart, and lungs. The clearance studies carried out over a period of 15 days indicated hepatobiliary excretion of the nanoparticles. Selected tissues were analyzed for any potential toxicity by histological analysis, which confirmed the absence of any adverse effect or any other abnormalities in the tissues. The results demonstrate that these multimodal nanoparticles have potentially ideal attributes for use as biocompatible probes for in vivo imaging.
| S-EPMC2827663 | biostudies-literature
Project description:ObjectiveFrontal plane knee alignment plays an integral role in tibiofemoral knee osteoarthritis development and progression. Accessible methods for obtaining direct or indirect measures of knee alignment may help inform clinical decision making when specialized equipment is unavailable. The present study evaluated the concurrent validity, as well as intersession (within-rater) and interrater (within-session) reliability of smartphone inclinometry for measuring static frontal plane tibial alignment-a known proxy of frontal plane knee alignment.MethodsTwenty healthy individuals and 38 patients with knee osteoarthritis were measured for frontal plane tibial alignment by a pair of raters using smartphone inclinometry, manual inclinometry, and 3-dimensional motion capture simultaneously. Healthy participants were measured on 2 separate days. Bland-Altman analysis, supplemented with intraclass correlation coefficient (ICC)(2,k), was used to assess concurrent validity. ICC(2,k), SEM, and minimum detectable change with 95% confidence limits (MDC95) were used to assess measurement reliability.ResultsCompared against motion capture, smartphone inclinometry measured frontal plane tibial alignment with a mean difference of 0.7 and 1.1 degrees (biased toward varus) for healthy participants and participants with knee osteoarthritis, respectively (ICC[2,k] ≥ 0.87). Smartphone inclinometry measurements demonstrated adequate intersession (within-rater) relative (ICC[2,k] = 0.91) and absolute (SEM = 0.7 degrees; MDC95 = 1.8 degrees) reliability, which outperformed manual inclinometry (ICC[2,k] = 0.85; SEM = 1.0 degrees; MDC95 = 2.6 degrees). Interrater (within-session) reliability of smartphone inclinometry was acceptable in both cohorts (ICC[2,k] = 0.93; SEM = 0.4 degrees to 1.2 degrees; MDC95 = 1.2 degrees to 3.2 degrees).ConclusionSmartphone inclinometry is sufficiently valid and reliable for measuring frontal plane tibial alignment in healthy individuals and patients with medial tibiofemoral knee osteoarthritis.ImpactSmartphones are readily accessible by clinicians and researchers. Our assessment of measurement validity and reliability supports the use of smartphone inclinometry as a clinically available tool to measure frontal plane tibial alignment without medical imaging or specialized equipment.
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Project description:Nanoparticles based on plant viruses are emerging biomaterials for medical applications such as drug delivery and imaging. Their regular structures can undergo genetic and chemical modifications to carry large payloads of cargos, as well as targeting ligands. Of several such platforms under development, only few have been characterized in vivo. We recently introduced the filamentous plant virus, potato virus X (PVX), as a new platform. PVX presents with a unique nanoarchitecture and is difficult to synthesize chemically.Here, we present a detailed analysis of PVX biodistribution and clearance in healthy mice and mouse tumor xenograft models using a combination of ex vivo whole-organ imaging, quantitative fluorescence assays and immunofluorescence microscopy.While up to 30% of the PVX signal was from the colon, mammary and brain tumor tissues, remaining particles were cleared by the reticuloendothelial system organs (the spleen and liver), followed by slower processing and clearance through the kidneys and bile.
| S-EPMC4169171 | biostudies-literature
Project description:Magnetic particle imaging (MPI) is an emerging tracer-based medical imaging modality that images non-radioactive, kidney-safe superparamagnetic iron oxide (SPIO) tracers. MPI offers quantitative, high-contrast and high-SNR images, so MPI has exceptional promise for applications such as cell tracking, angiography, brain perfusion, cancer detection, traumatic brain injury and pulmonary imaging. In assessing MPI's utility for applications mentioned above, it is important to be able to assess tracer short-term biodistribution as well as long-term clearance from the body. Here, we describe the biodistribution and clearance for two commonly used tracers in MPI: Ferucarbotran (Meito Sangyo Co., Japan) and LS-oo8 (LodeSpin Labs, Seattle, WA). We successfully demonstrate that 3D MPI is able to quantitatively assess short-term biodistribution, as well as long-term tracking and clearance of these tracers in vivo.
| S-EPMC5739049 | biostudies-literature
Project description:Protein cage nanoparticles have the potential to serve as multifunctional cell targeted, imaging and therapeutic platforms for broad applications in medicine. However, before they find applications in medicine, their biocompatibility in vivo needs to be demonstrated. We provide here baseline biodistribution information of two different spherical protein cage nanoplatforms, the 28 nm viral Cowpea chlorotic mottle virus (CCMV) and the 12 nm heat shock protein (Hsp) cage. In naive and immunized mice both nanoplatforms show similar broad distribution and movement throughout most tissues and organs, rapid excretion, the absence of long-term persistence within mice tissue and organs, and no overt toxicity after a single injection. These results suggest that protein cage based nanoparticles may serve as safe, biocompatible, nanoplatforms for applications in medicine.
| S-EPMC2676807 | biostudies-literature