Rapidly separating dissolving microneedles with sustained-release colchicine and stabilized uricase for simplified long-term gout management

Despite growing prevalence and incidence,the management of gout remains suboptimal.The intermittent nature of the gout makes the long-term urate-lowering therapy(ULT)particularly important for gout management.However,patients are reluctant to take medication day after day to manage incurable occasional gout flares,and suffer from possible long-term toxicity.Therefore,a safe and easy-tooperate drug delivery system with simple preparation for the long-term management of gout is very necessary.Here,a chitosan-containing sustained-release microneedle system co-loaded with colchicine and uricase liposomes were fabricated to achieve this goal.This microneedle system was confirmed to successfully deliver the drug to the skin and maintain a one-week drug retention.Furthermore,its powerful therapeutic potency to manage gout was investigated in both acute gouty and chronic gouty models.Besides,the drug co-delivery system could help avoid long-term daily oral colchicine,a drug with a narrow therapeutic index.This system also avoids mass injection of uricase by improving its stability,enhancing the clinical application value of uricase.In general,this two-drug system reduces the dosage of uricase and colchicine and improves the patient’s compliance,which has a strong clinical translation.

Preparation of New Uric Acid Sensors Based on Iodide Selective Electrode

An electrode for uric acid has been prepared by using an iodide selective electrode with the uricase enzyme. The iodide selective electrode used was prepared from 10% TDMAI and PVC according to our previous study. The enzyme was immobilized on the iodide electrode by holding it at pH 7 phosphate buffer for 20 min at room temperature. The H2O2 formed from the reaction of uric acid was determined from the decrease of iodide concentration that was present in the reaction cell. The potential change was linear in the 2 × 10-5 to 2 × 10-4 M uric acid concentration (3 - 34 mg uric acid/100ml blood) range. Uric acid contents of some blood samples were determined with the new electrode and consistency was obtained with a colorimetric method. The effects of pH, iodide concentration, the amount of enzyme immobilized and the operating temperature were studied. No interference of ascorbic acid, glucose and urea was observed.

Commentary:Gut microbiota reduce the risk of hyperuricemia and gout in the human body

Gout,a prevalent and painful metabolic disease often associated with obesity and aging,is caused by the deposition of urate crystals in joints,bones,or soft tissues1.Urate is an intermediate metabolite within the purine degradation pathway,predominantly derived from uric acid under physiological pH levels.Hyperuricemia occurs due to excessive uric acid production or insufficient excretion2,which is associated with various chronic diseases,including type 2 diabetes.