TY - JOUR
T1 - The Effect of Microbubble-Assisted Ultrasound on Molecular Permeability across Cell Barriers
AU - Rousou, Charis
AU - De Maar, Josanne
AU - Qiu, Boning
AU - Van Der Wurff-Jacobs, Kim
AU - Ruponen, Marika
AU - Urtti, Arto
AU - Oliveira, Sabrina
AU - Moonen, Chrit
AU - Storm, Gert
AU - Mastrobattista, Enrico
AU - Deckers, Roel
N1 - Funding Information:
Funding: This research was funded by the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie Grant Agreement No. 722717 (OCUTHER).
Publisher Copyright:
© 2022 by the authors.
PY - 2022/3
Y1 - 2022/3
N2 - The combination of ultrasound and microbubbles (USMB) has been applied to enhance drug permeability across tissue barriers. Most studies focused on only one physicochemical aspect (i.e., molecular weight of the delivered molecule). Using an in vitro epithelial (MDCK II) cell barrier, we examined the effects of USMB on the permeability of five molecules varying in molecular weight (182 Da to 20 kDa) and hydrophilicity (LogD at pH 7.4 from 1.5 to highly hydrophilic). Treatment of cells with USMB at increasing ultrasound pressures did not have a significant effect on the permeability of small molecules (molecular weight 259 to 376 Da), despite their differences in hydrophilicity (LogD at pH 7.4 from −3.2 to 1.5). The largest molecules (molecular weight 4 and 20 kDa) showed the highest increase in the epithelial permeability (3-7-fold). Simultaneously, USMB enhanced intracellular accumulation of the same molecules. In the case of the clinically relevant anti- C-X-C Chemokine Receptor Type 4 (CXCR4) nanobody (molecular weight 15 kDa), USMB enhanced paracellular permeability by two-fold and increased binding to retinoblastoma cells by five-fold. Consequently, USMB is a potential tool to improve the efficacy and safety of the delivery of drugs to organs protected by tissue barriers, such as the eye and the brain.
AB - The combination of ultrasound and microbubbles (USMB) has been applied to enhance drug permeability across tissue barriers. Most studies focused on only one physicochemical aspect (i.e., molecular weight of the delivered molecule). Using an in vitro epithelial (MDCK II) cell barrier, we examined the effects of USMB on the permeability of five molecules varying in molecular weight (182 Da to 20 kDa) and hydrophilicity (LogD at pH 7.4 from 1.5 to highly hydrophilic). Treatment of cells with USMB at increasing ultrasound pressures did not have a significant effect on the permeability of small molecules (molecular weight 259 to 376 Da), despite their differences in hydrophilicity (LogD at pH 7.4 from −3.2 to 1.5). The largest molecules (molecular weight 4 and 20 kDa) showed the highest increase in the epithelial permeability (3-7-fold). Simultaneously, USMB enhanced intracellular accumulation of the same molecules. In the case of the clinically relevant anti- C-X-C Chemokine Receptor Type 4 (CXCR4) nanobody (molecular weight 15 kDa), USMB enhanced paracellular permeability by two-fold and increased binding to retinoblastoma cells by five-fold. Consequently, USMB is a potential tool to improve the efficacy and safety of the delivery of drugs to organs protected by tissue barriers, such as the eye and the brain.
KW - Epithelial permeation
KW - Intracellular accumulation
KW - Microbubbles
KW - Nanobody
KW - Paracellular permeability
KW - Ultrasound
UR - http://www.scopus.com/inward/record.url?scp=85127397642&partnerID=8YFLogxK
U2 - 10.3390/pharmaceutics14030494
DO - 10.3390/pharmaceutics14030494
M3 - Article
C2 - 35335871
AN - SCOPUS:85127397642
SN - 1999-4923
VL - 14
JO - Pharmaceutics
JF - Pharmaceutics
IS - 3
M1 - 494
ER -