Unknown

Dataset Information

0

Systemic delivery of blood-brain barrier-targeted polymeric nanoparticles enhances delivery to brain tissue.


ABSTRACT: Delivery of therapeutic agents to the central nervous system is a significant challenge, hindering progress in the treatment of diseases such as glioblastoma. Due to the presence of the blood-brain barrier (BBB), therapeutic agents do not readily transverse the brain endothelium to enter the parenchyma. Previous reports suggest that surface modification of polymer nanoparticles (NPs) can improve their ability to cross the BBB, but it is unclear whether the observed enhancements in transport are large enough to enhance therapy. In this study, we synthesized two degradable polymer NP systems surface-modified with ligands previously suggested to improve BBB transport, and tested their ability to cross the BBB after intravenous injection in mice. All the NP preparations were able to cross the BBB, although generally in low amounts (<0.5% of the injected dose), which was consistent with prior reports. One NP produced significantly higher brain uptake (?0.8% of the injected dose): a block copolymer of polylactic acid and hyperbranched polyglycerol, surface modified with adenosine (PLA-HPG-Ad). PLA-HPG-Ad NPs provided controlled release of camptothecin, killing U87 glioma cells in culture. When administered intravenously in mice with intracranial U87 tumors, they failed to increase survival. These results suggest that enhancing NP transport across the BBB does not necessarily yield proportional pharmacological effects.

SUBMITTER: Saucier-Sawyer JK 

PROVIDER: S-EPMC4860350 | BioStudies | 2015-01-01

REPOSITORIES: biostudies

Similar Datasets

2014-01-01 | S-EPMC4062180 | BioStudies
2017-01-01 | S-EPMC5581224 | BioStudies
1000-01-01 | S-EPMC5498832 | BioStudies
2019-01-01 | S-EPMC6545685 | BioStudies
2014-01-01 | S-EPMC4156894 | BioStudies
2016-01-01 | S-EPMC5257033 | BioStudies
2018-01-01 | S-EPMC5773361 | BioStudies
1000-01-01 | S-EPMC6100052 | BioStudies
2016-01-01 | S-EPMC4881964 | BioStudies
1000-01-01 | S-EPMC4491652 | BioStudies