Prolonged Drug-Releasing Fibers Attenuate Alzheimer's Disease-like Pathogenesis

Salles, Geisa Nogueira and Calió, M.L. and Afewerki, S. and Pacheco-Soares, C. and Porcionatto, M. and Hölscher, Christian and Lobo, Anderson O. (2018) Prolonged Drug-Releasing Fibers Attenuate Alzheimer's Disease-like Pathogenesis. ACS Applied Materials and Interfaces, 10 (43). pp. 36693-36702. ISSN 1944-8244

Abstract

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.