Deformable gas-filled microbubbles targeted to P-selectin

Abstract

Ultrasound contrast microbubbles have been successfully targeted to a number of intravascular disease markers. We hypothesized that targeted delivery could be improved further, by making the microbubbles deformable, leading to increased microbubble-endothelium adhesion contact area and stabilized adhesion. Activated leukocytes utilize such strategy; they deform after binding to inflamed endothelium in the vasculature. Lipid-shell microbubbles were targeted to the endothelial inflammatory protein P-selectin with a monoclonal anti-P-selectin antibody attached to the microbubble shell. Deformable microbubbles were created by controlled pressurization with partial gas loss, which generated an average excess shell surface area of ∼30% and the formation of outward-projected wrinkles and folds. Targeted microbubble adhesion and deformability were assessed in the parallel plate flow chamber under shear flow. Sustained adhesion of deformable microbubbles at wall shear stresses between 0.4 and 1.35 dyn/cm 2 was consistently better than adhesion of wrinkle-free microbubbles. Over this shear range, targeted wrinkled microbubbles were deformed by shear flow, unlike wrinkle-free microbubbles. In a murine cremaster inflammation model, a significant improvement of deformable microbubble targeting was observed by intravital microscopy. Overall, the mechanical aspects of adhesion, such as particle shape, deformability and surface microstructure, are important in engineering efficient site-targeted particle-based agents for medical imaging and therapy.

Effects of high-fat diet and losartan on renal cortical blood flow using contrast ultrasound imaging

“…Volumetric imaging may therefore be required to achieve the greatest sensitivity, although at the expense of increased procedure time and complexity. Imaging in our study was performed using a clinical ultrasound scanner operating at 14 MHz, offering a spatial resolution of ϳ250 m. Ultra-high-frequency ultrasound, operating at 40 MHz and with a spatial resolution of ϳ100 um, can be used with microbubble contrast agents (51). However, as noted by Sullivan et al (57), the sensitivity to contrast agents using ultrahigh ultrasound scanners is generally limited.…”

Improving the Performance of Nano–Endofullerenes in Polyaniline Nanostructure–Based Biosensors by Covering Californium Colloidal Nanoparticles with Multi–Walled Carbon Nanotubes

“…This powder is the raw material for producing the electrode. CP (Carbon Paste) is produced by adding 100 (mg) of Carbon graphite powder to 36 (µl) of paraffin oil, according to [221][222][223][224][225][226][227][228][229][230][231]. The modified CP with Californium colloidal nanoparticles is produced by adding 300 (µl) of Californium colloidal nanoparticles to 100 (mg) of Carbon graphite powder and after evaporation of water in desiccator for 3 hours, 36 (µl) of paraffin oil is added to it.…”

Factors modulating the delivery and effect of enzymatic cargo conjugated with antibodies targeted to the pulmonary endothelium

“…Targeted drug delivery to the endothelium may help to improve treatment of diseases affecting the vasculature [1][2][3][4][5][6][7]. Targeted drug delivery systems (DDSs) designed to achieve this goal consist of affinity vectors (e.g., antibodies directed to endothelial surface determinants) coupled either directly to pharmacological cargoes (e.g., therapeutic enzymes) or to drugloaded vehicles or carriers (e.g., liposomes or polymer nanocarriers) [8][9][10][11][12][13][14].…”