Back to Search
Start Over
Protein-functionalized nanoparticles derived from end-functional polymers and polymer prodrugs for crossing the blood-brain barrier
- Source :
- European Journal of Pharmaceutics and Biopharmaceutics, European Journal of Pharmaceutics and Biopharmaceutics, Elsevier, 2019, 142, pp.70-82. ⟨10.1016/j.ejpb.2019.06.004⟩
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- Nanoparticles may provide a viable way for neuroprotective drugs to cross the blood-brain barrier (BBB), which limits the passage of most drugs from the peripheral circulation to the brain. Heterotelechelic polymer prodrugs comprising a neuroprotective model drug (adenosine) and a maleimide functionality were synthesized by the "drug-initiated" approach and subsequent nitroxide exchange reaction. Nanoparticles were obtained by nano-precipitation and exhibited high colloidal stability with diameters in the 162-185 nm range and narrow size distributions. Nanoparticles were then covalently surface-conjugated to different proteins (albumin, alpha 2-macroglobulin and fetuin A) to test their capability of enhancing BBB translocation. Their performances in terms of endothelial permeability and cellular uptake in an in vitro BBB model were compared to that of similar nano particles with surface-adsorbed proteins, functionalized or not with the drug. It was shown that bare NPs (i.e., NPs not surface-functionalized with proteins) without the drug exhibited significant permeability and cellular uptake, which were further enhanced by NP surface functionalization with alpha 2-macroglobulin. However, the presence of the drug at the polymer chain-end prevented efficient passage of all types of NPs through the BBB model, likely due to a decrease in the hydrophobicity of the nanoparticle surface and alteration of the protein binding/coupling, respectively. These results established a new and facile synthetic approach for the surface-functionalization of polymer nanoparticles for brain delivery purposes.
- Subjects :
- Polymers
Pharmaceutical Science
Nanoparticle
02 engineering and technology
Plasma protein binding
Blood–brain barrier
030226 pharmacology & pharmacy
Permeability
Cell Line
03 medical and health sciences
0302 clinical medicine
medicine
Humans
Prodrugs
Polymer
Prodrug
ComputingMilieux_MISCELLANEOUS
Drug Carriers
Chemistry
Brain
Proteins
Biological Transport
General Medicine
021001 nanoscience & nanotechnology
Fetuin
[CHIM.POLY]Chemical Sciences/Polymers
[SDV.SP.PG]Life Sciences [q-bio]/Pharmaceutical sciences/Galenic pharmacology
medicine.anatomical_structure
Blood-Brain Barrier
Drug delivery
Biophysics
Nanoparticles
Surface modification
Adsorption
Functional polymers
0210 nano-technology
Biotechnology
Subjects
Details
- ISSN :
- 09396411
- Volume :
- 142
- Database :
- OpenAIRE
- Journal :
- European Journal of Pharmaceutics and Biopharmaceutics
- Accession number :
- edsair.doi.dedup.....ec821224ce5d6922127757371b09f323