TY - CHAP
T1 - Biodegradable Polymeric Nanoparticles for Brain-Targeted Drug Delivery
AU - Kempe, Kristian
AU - Nicolazzo, Joseph A.
PY - 2021
Y1 - 2021
N2 - The blood-brain barrier (BBB), formed by endothelial cells lining the cerebral microvessels, remains a formidable challenge for the delivery of many therapeutics into the central nervous system (CNS). In an attempt to enhance the CNS disposition of therapeutics, which either have poor inherent permeability across the BBB or whose brain uptake is limited by the function of efflux transporters, a multitude of polymeric nanocarriers have been exploited. Common natural and synthetic polymers used for the development of these nanocarriers include polysaccharides, poly(alkylcyanoacrylate)s, and polyesters such as poly(lactic-co-glycolic acid). To avoid recognition by circulating macrophages and, therefore, minimize their systemic clearance, these polymeric nanocarriers are often coated with polyethylene glycol or emulsifiers such as polysorbate 80, and to enhance their targeting to the BBB, addition of various targeting entities such as antibodies to brain microvascular receptor-mediated transporters is common. Unlike liposomes however, polymeric nanoparticles are more stable, allow for a detailed control of the carrier properties (e.g., size, shape, charge, surface morphology and chemistry), facilitate the delivery of a range of different cargoes with high capacities, and can be engineered with different drug release mechanisms and modified with various targeting ligands. This chapter will provide an up-to-date account on the various polymeric nanoparticle approaches which have been exploited to target therapeutics to the CNS, with particular focus on biodegradable polymers and practical techniques that can be employed for the preparation of these polymeric nanoparticles.
AB - The blood-brain barrier (BBB), formed by endothelial cells lining the cerebral microvessels, remains a formidable challenge for the delivery of many therapeutics into the central nervous system (CNS). In an attempt to enhance the CNS disposition of therapeutics, which either have poor inherent permeability across the BBB or whose brain uptake is limited by the function of efflux transporters, a multitude of polymeric nanocarriers have been exploited. Common natural and synthetic polymers used for the development of these nanocarriers include polysaccharides, poly(alkylcyanoacrylate)s, and polyesters such as poly(lactic-co-glycolic acid). To avoid recognition by circulating macrophages and, therefore, minimize their systemic clearance, these polymeric nanocarriers are often coated with polyethylene glycol or emulsifiers such as polysorbate 80, and to enhance their targeting to the BBB, addition of various targeting entities such as antibodies to brain microvascular receptor-mediated transporters is common. Unlike liposomes however, polymeric nanoparticles are more stable, allow for a detailed control of the carrier properties (e.g., size, shape, charge, surface morphology and chemistry), facilitate the delivery of a range of different cargoes with high capacities, and can be engineered with different drug release mechanisms and modified with various targeting ligands. This chapter will provide an up-to-date account on the various polymeric nanoparticle approaches which have been exploited to target therapeutics to the CNS, with particular focus on biodegradable polymers and practical techniques that can be employed for the preparation of these polymeric nanoparticles.
KW - Blood-brain barrier
KW - Nanoparticle
KW - PLGA
KW - Polymer
KW - Surface coating
KW - Targeting
UR - http://www.scopus.com/inward/record.url?scp=85096511445&partnerID=8YFLogxK
U2 - 10.1007/978-1-0716-0838-8_1
DO - 10.1007/978-1-0716-0838-8_1
M3 - Chapter (Book)
AN - SCOPUS:85096511445
SN - 9781071608371
T3 - Neuromethods
SP - 1
EP - 27
BT - Nanomedicines for Brain Drug Delivery
A2 - Morales, Javier O
A2 - Gaillard, Pieter J
PB - Humana Press
CY - New York NY USA
ER -