Dataset Information

The clearance and biodistribution of magnetic composite nanoparticles in healthy and osteoarthritic rat knees.

ABSTRACT: Intra-articular injections are the most direct route for administering osteoarthritis (OA) therapies, yet how drug carriers distribute within the joint remains understudied. To this end, we developed a magnetic composite nanoparticle that can be tracked with fluorescence in vivo via an in vivo imaging system (IVIS), and quantified ex vivo via electron paramagnetic resonance (EPR) spectroscopy. Using this particle, the effects of age and OA pathogenesis on particle clearance and distribution were evaluated in the medial meniscus transection model of OA (5-, 10-, and 15-month old male Lewis rats). At 9 weeks after meniscus transection, composite nanoparticles were injected and joint clearance was assessed via IVIS. At 2 weeks after injection, animals were euthanized and particle distribution was quantified ex vivo via EPR spectroscopy. IVIS and EPR spectroscopy data indicate a predominant amount of particles remained in the joint after 14 days. EPR spectroscopy data suggests particles cleared more slowly from OA knees than from the contralateral control, with particles clearing more slowly from 15-month old rats than from 5- and 10-month old rats. This study demonstrates the importance of including both age and OA as factors when evaluating nanoparticles for intra-articular drug delivery.

SUBMITTER: Partain BD

PROVIDER: S-EPMC7942179 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The clearance and biodistribution of magnetic composite nanoparticles in healthy and osteoarthritic rat knees.

Partain Brittany D BD Unni Mythreyi M Rinaldi Carlos C Allen Kyle D KD

Journal of controlled release : official journal of the Controlled Release Society 20200128

Intra-articular injections are the most direct route for administering osteoarthritis (OA) therapies, yet how drug carriers distribute within the joint remains understudied. To this end, we developed a magnetic composite nanoparticle that can be tracked with fluorescence in vivo via an in vivo imaging system (IVIS), and quantified ex vivo via electron paramagnetic resonance (EPR) spectroscopy. Using this particle, the effects of age and OA pathogenesis on particle clearance and distribution were ...[more]

PMID: 32004585

Similar Datasets

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.

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.

Project description:Frontal 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. Twenty 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. Compared 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). Smartphone inclinometry is sufficiently valid and reliable for measuring frontal plane tibial alignment in healthy individuals and patients with medial tibiofemoral knee osteoarthritis. Smartphones 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.

Dataset Information

The clearance and biodistribution of magnetic composite nanoparticles in healthy and osteoarthritic rat knees.

Publications

The clearance and biodistribution of magnetic composite nanoparticles in healthy and osteoarthritic rat knees.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets