Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Prolonged Drug-Releasing Fibers Attenuate Alzheimer's Disease-like Pathogenesis
AU - Salles, Geisa Nogueira
AU - Calió, M.L.
AU - Afewerki, S.
AU - Pacheco-Soares, C.
AU - Porcionatto, M.
AU - Hölscher, Christian
AU - Lobo, Anderson O.
PY - 2018/10/31
Y1 - 2018/10/31
N2 - Delivering drugs and agents to the brain is a huge challenge, especially for chronic neurodegenerative disorders, such as Alzheimer's disease (AD). For this, prolonged and sustained release methods to increase brain uptake represent an impacting concept. The bioresorbable polymer poly-lactic acid (PLA) has high potential for medical implants; at the same time, glucagon-like peptide-1 (GLP-1) analogues have considerable neuroprotective attributes and represent a therapeutic strategy for AD. Here, a biodevice is produced by electrospinning PLA with a GLP-1 analogue (liraglutide, LG), coated with a thin layer of gelatin. The biodevice is subcutaneously implanted in a transgenic mouse model of AD and LG is released for 14 days in mice serum. After 4 weeks of implantation, crucial hallmarks of the AD are highly diminished: hippocampal senile amyloid β plaque load and neuroinflammatory markers. Furthermore, neurogenesis is enhanced in the subventricular zone, an important neurogenic niche in the brain. The designed biodevice holds great promise for being an affordable candidate to act as a prolonged drug provider, promoting LG mission through increasing its lifetime, constituting a relevant approach for old and impaired brain. © 2018 American Chemical Society.
AB - Delivering drugs and agents to the brain is a huge challenge, especially for chronic neurodegenerative disorders, such as Alzheimer's disease (AD). For this, prolonged and sustained release methods to increase brain uptake represent an impacting concept. The bioresorbable polymer poly-lactic acid (PLA) has high potential for medical implants; at the same time, glucagon-like peptide-1 (GLP-1) analogues have considerable neuroprotective attributes and represent a therapeutic strategy for AD. Here, a biodevice is produced by electrospinning PLA with a GLP-1 analogue (liraglutide, LG), coated with a thin layer of gelatin. The biodevice is subcutaneously implanted in a transgenic mouse model of AD and LG is released for 14 days in mice serum. After 4 weeks of implantation, crucial hallmarks of the AD are highly diminished: hippocampal senile amyloid β plaque load and neuroinflammatory markers. Furthermore, neurogenesis is enhanced in the subventricular zone, an important neurogenic niche in the brain. The designed biodevice holds great promise for being an affordable candidate to act as a prolonged drug provider, promoting LG mission through increasing its lifetime, constituting a relevant approach for old and impaired brain. © 2018 American Chemical Society.
KW - Alzheimer's disease
KW - biodevice
KW - liraglutide
KW - poly-lactic acid fibers
KW - prolonged release
KW - Controlled drug delivery
KW - Functional polymers
KW - Lactic acid
KW - Mammals
KW - Polymeric implants
KW - Targeted drug delivery
KW - Biodevice
KW - Liraglutide
KW - Poly lactic acid fibers
KW - Prolonged release
KW - Neurodegenerative diseases
U2 - 10.1021/acsami.8b12649
DO - 10.1021/acsami.8b12649
M3 - Journal article
VL - 10
SP - 36693
EP - 36702
JO - ACS Applied Materials and Interfaces
JF - ACS Applied Materials and Interfaces
SN - 1944-8244
IS - 43
ER -