Alzheimer’s disease(AD)is a progressive neurodegenerative disease with a complex etiology.The main neu-ropathological feature is the accumulation of amyloid-beta(Aβ),and the dysregulation of the cholinergic system i...Alzheimer’s disease(AD)is a progressive neurodegenerative disease with a complex etiology.The main neu-ropathological feature is the accumulation of amyloid-beta(Aβ),and the dysregulation of the cholinergic system is well associated with its mechanism of occurrence,for which no effective treatment is yet available.Daily oral administration remains the mainstay of treatment with AD,and how to improve the efficacy,prolong adsorp-tion and medication compliance is still the focus of the current solution.We proposed a microcapsule based on microfluidic electrospray to form an intestinal epithelial lining for AD treatment,reducing the frequency of administration.Microfluidic electrospray technology was recruited to overcome the limitations associated with the variability in the microencapsulation production process and to produce functional microcapsules with finely adapted chemical composition,capsule thickness and encapsulant volume ratio.These microcapsules could slowly release drugs after adhering to the intestine,and their effectiveness and safety were further evaluated using cell culture studies and animal model studies.The results from the in vivo and in vitro experiments showed a significant reduction in administration frequency(i.e.,from daily medication to once every five days),superior therapeutic efficacy and sufficient safety of these microcapsules in cell culture and APP/PS1 mice.These features make the microcapsules an excellent drug delivery system and represent great potential for clinical applications in AD.展开更多
基金This work was supported partly by grants from the National Natu-ral Science Foundation of China(No.82071186)Clinical Trials from the Affiliated Drum Tower Hospital,Medical School of Nanjing Univer-sity(No.2022-LCYG-MS-05)+1 种基金National Key Research and Development Program of China(No.2022YFA1105300)Jiangsu Province Senior Health Project(No.LKZ2023014).
文摘Alzheimer’s disease(AD)is a progressive neurodegenerative disease with a complex etiology.The main neu-ropathological feature is the accumulation of amyloid-beta(Aβ),and the dysregulation of the cholinergic system is well associated with its mechanism of occurrence,for which no effective treatment is yet available.Daily oral administration remains the mainstay of treatment with AD,and how to improve the efficacy,prolong adsorp-tion and medication compliance is still the focus of the current solution.We proposed a microcapsule based on microfluidic electrospray to form an intestinal epithelial lining for AD treatment,reducing the frequency of administration.Microfluidic electrospray technology was recruited to overcome the limitations associated with the variability in the microencapsulation production process and to produce functional microcapsules with finely adapted chemical composition,capsule thickness and encapsulant volume ratio.These microcapsules could slowly release drugs after adhering to the intestine,and their effectiveness and safety were further evaluated using cell culture studies and animal model studies.The results from the in vivo and in vitro experiments showed a significant reduction in administration frequency(i.e.,from daily medication to once every five days),superior therapeutic efficacy and sufficient safety of these microcapsules in cell culture and APP/PS1 mice.These features make the microcapsules an excellent drug delivery system and represent great potential for clinical applications in AD.
