| DOI | Resolve DOI: https://doi.org/10.1021/mp3004995 |
|---|
| Author | Search for: Haqqani, A.S.1; Search for: Caram-Salas, N.1; Search for: Ding, W.1; Search for: Brunette, E.1; Search for: Delaney, C.E.1; Search for: Baumann, E.1; Search for: Boileau, E.1; Search for: Stanimirovic, D.1 |
|---|
| Affiliation | - National Research Council of Canada. Human Health Therapeutics
|
|---|
| Format | Text, Article |
|---|
| Subject | FC44 antibody; FC5 antibody; nanobody; peptides and proteins; unclassified drug; animal cell; animal experiment; animal tissue; binding affinity; blood brain barrier; blood cerebrospinal fluid barrier; brain cell; brain endothelial cell; cerebrospinal fluid; drug cerebrospinal fluid level; endothelium cell; fluorescence imaging; human cell; in vitro study; isotope labeling; limit of detection; limit of quantitation; male; microvascular endothelial cell; molecular weight; nucleotide sequence; outcome assessment; phage display; plasma half life; treatment duration |
|---|
| Abstract | FC5 and FC44 are single-domain antibodies (VHHs), selected by functional panning of phage-display llama VHH library for their ability to internalize human brain endothelial cells (BEC) and to transmigrate the in vitro BBB model. Quantification of brain delivery of FC5 and FC44 in vivo was challenging using classical methods because of their short plasma half-life and their loss of functionality with radioactive labeling. A highly sensitive (detection limit <2 ng/mL) and specific SRM-ILIS method to detect and quantify unlabeled VHHs in multiplexed assays was developed and applied to comparatively evaluate brain delivery of FC5 and FC44, and two control VHHs, EG2 and A20.1. FC5 and FC44 compared to control V HHs demonstrated significantly (p < 0.01) enhanced transport (50-100-fold) across rat in vitro BBB model as well as in vivo brain targeting assessed by optical imaging. The multiplexed SRM-ILIS analyses of plasma and CSF levels of codosed VHHs demonstrated that while all 4 VHHs have similar blood pharmacokinetics, only FC5 and FC44 show elevated CSF levels, suggesting that they are potential novel carriers for delivery of drugs and macromolecules across the BBB. © Published 2012 by the American Chemical Society. |
|---|
| Publication date | 2013 |
|---|
| In | |
|---|
| Language | English |
|---|
| Peer reviewed | Yes |
|---|
| NPARC number | 21269642 |
|---|
| Export citation | Export as RIS |
|---|
| Report a correction | Report a correction (opens in a new tab) |
|---|
| Record identifier | 0d951595-1ff4-4447-965c-44d5a9dc3e9c |
|---|
| Record created | 2013-12-13 |
|---|
| Record modified | 2020-04-22 |
|---|
