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,...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.展开更多
基金the financial support from the National Natural Science Foundation(NOs.32071342,and 82272154,China)Guangdong Special Support Program(NO.2019TQ05Y209,China)+5 种基金the Natural Science Foundation of Guangdong Province(NO.2023A1515012015,China)Tianjin Science Fund for Distinguished Young Scholars(NO.22JCJQJC00120,China)Natural Science Foundation of Tianjin(The Basic Research Cooperation Special Foundation of Beijing-Tianjin-Hebei Region,NO.22JCZXJC00060,China)the Fundamental Research Funds for the Central Universities(NO.2021-RC310-005,China)Technology&Innovation Commission of Shenzhen Municipality(NOs.JCYJ20220818102810023,JCYJ20190807153601667,and JCYJ20210324124402006,China)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(NOs.2021-I2M-1e058,and 2022-I2M-2-003,China)。
文摘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.
