Abstract:
Ultrasound as a non-invasive and non-ionizing technology has been utilized as an efficient
technique for the transport of drugs and genes in addition to its use of imaging. Sonoporation
(cavitation generation by microbubbles), one of the applications of ultrasound contrast agents has
been utilized as an effective approach for the opening of the blood-brain barrier. In combination
with the targeted microbubbles, these act as effective delivery vehicles for the transport of anti tumor drugs to enhance drug uptake and enhance the treatment of Glioblastoma multiforme. In
this study, we have designed gH625-tagged microbubbles which can cross the blood-brain barrier
by adsorption mechanism. These microbubbles were synthesized by the solvent displacement
method and were linked to the membrane crossing peptide (gH625). Two types of microbubbles
were synthesized: core-containing Cisplatin microbubbles and shell-encapsulating Amygdalin
microbubbles, as microbubbles had core and shell pockets for drug loading. These pre-PGS,
gH625-tagged microbubbles were characterized through FTIR and SEM analysis. Microbubbles
were taken by the glial cells one of the components of BBB and have been able to be uptake by
the U-87 cell line (a glioblastoma multiforme cell line). Cell viability was analyzed and compared
with the bare drug. Upon ultrasound exposure, the overall cytotoxic activity of anti-tumor drugs
loaded pre-PGS microbubbles alleviated as cavitation nuclei enhanced the uptake of the drug
while reducing the systemic side effects. Thus, ultrasound-mediated gH625 tagged pre-PGS
microbubbles not only helps to open the BBB by generating reversible gaps in the endothelial layer
of the BBB but also enhance the anti-neoplastic activity in addition to the safe delivery carrier
function of the microbubbles, minimizing the side effects of the drugs
