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Development of color changing polydiacetylene-based biomimetic nanovesicle platforms for quick detection of membrane permeability across the blood brain barrier.
- Source :
-
Nanoscale [Nanoscale] 2020 Apr 28; Vol. 12 (16), pp. 8898-8908. Date of Electronic Publication: 2020 Apr 08. - Publication Year :
- 2020
-
Abstract
- Membrane permeability through passive diffusion is one of the important pathways for passage of drugs across the blood brain barrier (BBB). The present study describes the development of biomimetic unilamellar lipopolymeric nanovesicles of size 268 ± 37 nm, consisting of polar brain lipids in conjunction with polydiacetylene and validation of their application for an abbreviated yet accurate membrane permeability assay with high-throughput and rapid identification of BBB permeability of drugs. The nanovesicle suspension was tested with drugs of known permeability across the BBB to validate the detection of changes in hue, absorbance and fluorescence in response to permeation across the nanovesicles. A simple device was developed based on the nanovesicle sensors along with a mobile application which allowed for the determination of hue corresponding to qualitative identification of whether a drug is BBB permeable (BBB+) or not (BBB-). With respect to determination of a suitable endpoint in this assay, a hue cut off of 275°, reduction in %blueness by less than 59% and a fluorescence intensity of ≥0.22 a.u. at 560 nm accurately differentiated between drugs which are permeable and impermeable across the BBB within 5 minutes. Further quantification of BBB permeability can be done through the concentration at which the above end-points are achieved. For the quantification of the permeability, absorbance and fluorescence measurements were performed. The device thus developed allows the rapid determination of BBB permeability of various agents in drug discovery especially in smaller set-ups with minimal equipment through changes in color, absorbance and fluorescence.
- Subjects :
- Animals
Blood-Brain Barrier drug effects
Brain metabolism
Drug Carriers chemistry
Drug Carriers pharmacology
Goats
Lipids chemistry
Membranes, Artificial
Microscopy, Fluorescence
Particle Size
Ultraviolet Rays
Verapamil chemistry
Verapamil metabolism
Biomimetic Materials chemistry
Blood-Brain Barrier metabolism
Nanostructures chemistry
Permeability drug effects
Polyacetylene Polymer chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 2040-3372
- Volume :
- 12
- Issue :
- 16
- Database :
- MEDLINE
- Journal :
- Nanoscale
- Publication Type :
- Academic Journal
- Accession number :
- 32266882
- Full Text :
- https://doi.org/10.1039/c9nr07845b