Efficient oral delivery of drugs treating brain diseases has long been a challenging topic faced by the drug delivery community. Fortunately, polyester nanoparticles offer certain solutions to this problem. This revie...Efficient oral delivery of drugs treating brain diseases has long been a challenging topic faced by the drug delivery community. Fortunately, polyester nanoparticles offer certain solutions to this problem. This review article firstly describes the main obstacles faced by oral administered brain targeting, including:(1)instability in the gastrointestinal tract;(2) poor penetration of the intestinal mucosa and epithelium;(3)blood clearance;and(4) restriction by the BBB. Then the key factors influencing brain-targeting efficiency of orally administered polyester nanoparticles are also discussed, such as size, shape and surface properties. Finally, recent brain-targeting delivery strategies using oral polyester nanoparticles as carriers and their effects on brain drugs transport are reviewed, and the delivery ‘as a whole’ strategy of polyester nanoparticles will provide new insight for oral brain-targeting delivery. And by combination of multiple strategies, both the stability and permeability of polyester nanoparticles can be greatly improved for oral brain drug delivery.展开更多
The existence of the blood-brain barrier(BBB)restricts the entry of drugs from the circulation into the central nervous system(CNS),which severely affects the treatment of neurological diseases,including glioblastoma,...The existence of the blood-brain barrier(BBB)restricts the entry of drugs from the circulation into the central nervous system(CNS),which severely affects the treatment of neurological diseases,including glioblastoma,Parkinson’s disease(PD),and Alzheimer’s disease(AD).With the advantage of bypassing the BBB and avoiding systemic distribution,intranasal administration has emerged as an alternative method of delivering drugs to the brain.Drug delivery directly to the brain using intranasal nanosystems represents a new paradigm for neurological disease treatment because of its advantages in improving drug solubility and stability in vivo,enabling targeted drug delivery and controlled release,and reducing non-specific toxicity.And it has shown efficacy in animal models and clinical applications.Herein,this review describes the mechanisms of intranasal delivery of brain-targeted drugs,the properties of nanosystems for intranasal administration(e.g.,liposomes,nanoemulsions,and micelles),and strategies for intranasal drug delivery to enhance brain-targeted drug delivery.Recent applications of nanosystems in intranasal drug delivery and disease treatment have been comprehensively reviewed.Although encouraging results have been reported,significant challenges still need to be overcome to translate these nanosystems into clinics.Therefore,the future prospects of intranasal drug delivery nanosystems are discussed in depth,expecting to provide useful insights and guidance for effective neurological disease treatment.展开更多
There has been a lot of basic and clinical research on Alzheimer’s disease(AD)over the last 100 years,but its mechanisms and treatments have not been fully clarified.Despite some controversies,the amyloid-beta hypoth...There has been a lot of basic and clinical research on Alzheimer’s disease(AD)over the last 100 years,but its mechanisms and treatments have not been fully clarified.Despite some controversies,the amyloid-beta hypothesis is one of the most widely accepted causes of AD.In this study,we disclose a new amyloid-beta plaque disaggregating agent and an AD brain-targeted delivery system using porous silicon nanoparticles(pSiNPs)as a therapeutic nano-platform to overcome AD.We hypothesized that the negatively charged sulfonic acid functional group could disaggregate plaques and construct a chemical library.As a result of the in vitro assay of amyloid plaques and library screening,we confirmed that 6-amino-2-naphthalenesulfonic acid(ANA)showed the highest efficacy for plaque disaggregation as a hit compound.To confirm the targeted delivery of ANA to the AD brain,a nano-platform was created using porous silicon nanoparticles(pSiNPs)with ANA loaded into the pore of pSiNPs and biotin-polyethylene glycol(PEG)surface functionalization.The resulting nano-formulation,named Biotin-CaCl2-ANA-pSiNPs(BCAP),delivered a large amount of ANA to the AD brain and ameliorated memory impairment of the AD mouse model through the disaggregation of amyloid plaques in the brain.This study presents a new bioactive small molecule for amyloid plaque disaggregation and its promising therapeutic nano-platform for AD brain-targeted delivery.展开更多
基金supported by the National Key R&D Program of China (No. 2020YFE0201700)the National Mega-project for Innovative Drugs (No. 2019ZX09721001)+3 种基金the National Natural Science Foundation of China (No. 81673378)the Liaoning Revitalization Talents Program (No. XLYC1908031)the Project of Liaoning Provincial Department of Education (No. 2019LQN07)the PhD Research Startup Foundation of Liaoning Province (No. 2020-BS-128)。
文摘Efficient oral delivery of drugs treating brain diseases has long been a challenging topic faced by the drug delivery community. Fortunately, polyester nanoparticles offer certain solutions to this problem. This review article firstly describes the main obstacles faced by oral administered brain targeting, including:(1)instability in the gastrointestinal tract;(2) poor penetration of the intestinal mucosa and epithelium;(3)blood clearance;and(4) restriction by the BBB. Then the key factors influencing brain-targeting efficiency of orally administered polyester nanoparticles are also discussed, such as size, shape and surface properties. Finally, recent brain-targeting delivery strategies using oral polyester nanoparticles as carriers and their effects on brain drugs transport are reviewed, and the delivery ‘as a whole’ strategy of polyester nanoparticles will provide new insight for oral brain-targeting delivery. And by combination of multiple strategies, both the stability and permeability of polyester nanoparticles can be greatly improved for oral brain drug delivery.
基金supported by the STI 2030-Major Projects(No.2021ZD0201602).
文摘The existence of the blood-brain barrier(BBB)restricts the entry of drugs from the circulation into the central nervous system(CNS),which severely affects the treatment of neurological diseases,including glioblastoma,Parkinson’s disease(PD),and Alzheimer’s disease(AD).With the advantage of bypassing the BBB and avoiding systemic distribution,intranasal administration has emerged as an alternative method of delivering drugs to the brain.Drug delivery directly to the brain using intranasal nanosystems represents a new paradigm for neurological disease treatment because of its advantages in improving drug solubility and stability in vivo,enabling targeted drug delivery and controlled release,and reducing non-specific toxicity.And it has shown efficacy in animal models and clinical applications.Herein,this review describes the mechanisms of intranasal delivery of brain-targeted drugs,the properties of nanosystems for intranasal administration(e.g.,liposomes,nanoemulsions,and micelles),and strategies for intranasal drug delivery to enhance brain-targeted drug delivery.Recent applications of nanosystems in intranasal drug delivery and disease treatment have been comprehensively reviewed.Although encouraging results have been reported,significant challenges still need to be overcome to translate these nanosystems into clinics.Therefore,the future prospects of intranasal drug delivery nanosystems are discussed in depth,expecting to provide useful insights and guidance for effective neurological disease treatment.
基金supported by Basic Science Research Program through the National Research Foundation(NRF)of Korea funded by the Ministry of Education(2018-R1A6A1A03025124D.K.)+5 种基金supported by Bio&Medical Technology Development Program of the NRF of Korea funded by the Ministry of Science&ICT(2022-M3A9H1014157,2021-M3A9I5030523D.K.)a grant from Korea Health Technology R&D Project of the Korea Health Industry Development Institute(KHIDI)funded by the Ministry of Health&Welfare,Republic of Korea(HI21C0239D.K.)supported by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(2022-R1F1A1069954D.K.).
文摘There has been a lot of basic and clinical research on Alzheimer’s disease(AD)over the last 100 years,but its mechanisms and treatments have not been fully clarified.Despite some controversies,the amyloid-beta hypothesis is one of the most widely accepted causes of AD.In this study,we disclose a new amyloid-beta plaque disaggregating agent and an AD brain-targeted delivery system using porous silicon nanoparticles(pSiNPs)as a therapeutic nano-platform to overcome AD.We hypothesized that the negatively charged sulfonic acid functional group could disaggregate plaques and construct a chemical library.As a result of the in vitro assay of amyloid plaques and library screening,we confirmed that 6-amino-2-naphthalenesulfonic acid(ANA)showed the highest efficacy for plaque disaggregation as a hit compound.To confirm the targeted delivery of ANA to the AD brain,a nano-platform was created using porous silicon nanoparticles(pSiNPs)with ANA loaded into the pore of pSiNPs and biotin-polyethylene glycol(PEG)surface functionalization.The resulting nano-formulation,named Biotin-CaCl2-ANA-pSiNPs(BCAP),delivered a large amount of ANA to the AD brain and ameliorated memory impairment of the AD mouse model through the disaggregation of amyloid plaques in the brain.This study presents a new bioactive small molecule for amyloid plaque disaggregation and its promising therapeutic nano-platform for AD brain-targeted delivery.
