Effects of nanoparticles on gouty arthritis in animal models of gout

By Neha MathurReviewed by Danielle Ellis, B.Sc.Feb 23 2023

In a recent study published in the BMC Musculoskeletal Disorders, researchers performed a systematic review and meta-analysis to explore the effects of nanoparticles on gouty arthritis using animal models. Based on this work, the researchers proposed testing nanomedicine-based treatment ideas for gouty arthritis in clinical studies.

Background

Excessive monosodium urate (MSU) deposition due to increased blood uric acid levels causes an inflammatory condition called gouty arthritis. The prevalence of this disease is increasing globally, with epidemiological studies reporting global prevalence rates between 0.02% and 6.8%.

About the study

In the present study, two researchers independently searched published scientific literature (in the English language) from five databases, e.g., Scopus and Embase, till April 2022 to identify studies that met the eligibility criteria. All eligible studies used an animal-based gouty arthritis model. They used nanoparticles as a therapeutic intervention, while their control groups used allopurinol and indomethacin. The primary outcome of these studies was the serum uric acid level or the extent of swelling in joints.

They used the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) 's risk of bias (RoB) tool to assess the risk of bias in the included studies, where 'no' and 'yes' indicated a high and low risk of bias, respectively, while the remaining were tagged 'unclear'. The team considered a study high quality only when it had no more than one unclear risk.

The team defined the effect sizes of this meta-analysis as the weighted mean difference (WMD) and the 95% confidence interval (CI). They used I² statistics to assess the heterogeneity of the pooled results, where an I² value between 50% to 100% indicated high heterogeneity. Finally, they explored the source of heterogeneity through subgroup analyses.

Results

The current systematic review covered 10 studies, all of which were quasi-experiments, and four of these provided specific data for the meta-analysis. Five of these 10 studies had only male animals, whereas the remaining five had both male and female animals. Seven studies used allopurinol as a control medication, and two and one used indomethacin and self-control before and after the intervention, respectively. Per RoB tool evaluation, all studies showed a higher risk of bias, of which nine and one studies were of medium and low quality, respectively.

The study results showed that though nanoparticles reduced uric acid levels in the serum of patients with gouty arthritis, they did not fetch better results than allopurinol. However, they had fewer side effects on kidney and liver functions and lipid profile and were safer for gouty arthritis patients. In addition, nanoparticles reduced joint swelling and ankle diameter.

Other advantages of nanoparticles for gouty arthritis are as follows:

i)  Nanoparticles mainly rely on the pharmacological properties of the entrapped materials and the transfer of nanomaterial shells. These substances were analgesic, had anti-inflammation properties, and controlled oxidative stress. The nanomaterial shell prolonged the biological half-life and improved the pharmacokinetics of encapsulated substances to maximize their therapeutic effect.

ii) Nanoparticles improved the bioavailability of medications. For instance, a study by Win et al. showed how nanoparticles using Vitamin E-succinated polyethylene glycol 1000 emulsified in D, L-lactic-co-glycolic acid improved the therapeutic index of the paclitaxel drug formulation. In addition, nanoparticles, especially non-metals-based nanoparticles, showed better water solubility and higher bioavailability than non-metallic herbal medicines (e.g., turmeric).

iii) Nanoparticles were safer than allopurinol and had fewer side effects on the kidney and liver, reflecting their non-toxicity to non-target organs. Though several nanoparticles in studies covered in this review caused liver inflammation caused due to bile duct blockage, studies should further review this finding for clarity.

Another study presented a remarkable example of a nanoparticle safety profile. In this study, copper sulfate (CuSO₄) slightly reduced the uric acid level in gout-affected test animals but damaged liver function. However, its entrapment in the nanoparticles significantly reduced uric acid levels and caused lesser damage to the kidney and liver.

Overall, nanoparticles effectively reduced the toxicity of some therapeutic substances used in gouty arthritis treatment. Furthermore, the authors noted that other factors, such as the number of animals used in the studies, their species, gender, etc., also affected the nanoparticle performance. For instance, among all animals, chicken served as an ideal model for studying gouty arthritis when injected with MSU in their left ankle joint. Other animals, such as mice, rabbits, and zebrafish, also served as gout model animals.

Studies in humans have shown that the incidence of gouty arthritis in women is higher than in men because its occurrence might be related to decreased estrogen levels, which makes postmenopausal women more prone to this disease. Accordingly, the gout treatment effect on mixed males and females test animals was more than only on males.

Conclusions

Though the findings of this meta-analysis were inconclusive, and the development of nanomedicine for gouty arthritis is in the nascent stages, this study could be a ready reference for its further development.

Nonetheless, the study established several advantages of using nanoparticles. They entrapped therapeutic substances in a manner that reduced their loss before reaching the designated site of action. They also increased their bioavailability to enable maximum utilization of the drug in the target organ, which, in addition, reduced the negative and promoted the therapeutic effects of the encapsulated substances on gouty arthritis.

In the future, nanoparticles might effectively treat gouty arthritis because of their safety and efficacy. However, there is an urgent need for well-designed preclinical and clinical trials demonstrating their effectiveness in larger sample sizes over a prolonged period.

Researchers should continue investigating the optimum medication dose of nanoparticle-based drugs. Since they observed high heterogeneity in animal quantity across all included studies, which affects the applicability of the experiment, the researchers also emphasized the need for determining fitting animal numbers for nanomedicine experiments.