Biomedical imaging and drug carriers

Use Cases 

What is the impact of the gaseous phase on the adsorption of HFBII at the air/water interface? 

Reference: Gazzera, L.; Milani, R.; Pirrie, L.; Schmutz, M.; Blanck, C.; Resnati, G.; Metrangolo, P.; Krafft, M. P., Design of highly stable echogenic microbubbles through controlled assembly of their hydrophobin shell. Angewandte Chemie 2016, 128 (35), 10419-10423.

Microbubbles are used as ultrasound contrast agents (UCAs) in biomedical imaging and need to be highly stable. Hydrophobins are a class of cysteine rich proteins used by the authors to stabilize µ-bubbles. Using an automatic drop tensiometer, TRACKER™ by TECLIS, the authors performed surface tension measurements that showed that F-hexane saturated-air resulted in a faster adsorption kinetics of hydrophobin HFBII and in a smaller equilibrium surface tension. Moreover, F-hexane decreased the viscoelastic modulus of the surface film. In summary, exposure to F-hexane enables the efficient, quasi-exclusive formation of homogenous, narrowly dispersed populations of spherical stable and echogenic µ-bubbles.

TECLIS product: TRACKER™ automatic drop tensiometer

Key words: fluorinated gas, microbubbles, stability, surface tension, fluid-to-solid transition, 2D viscoelasticity.

How to improve the stability of protein drug products by the addition of surfactants ? 

Reference: Katz, J. S.; Nolin, A.; Yezer, B. A.; Jordan, S., Dynamic properties of novel excipient suggest mechanism for improved performance in liquid stabilization of protein biologics. Molecular pharmaceutics 2018, 16 (1), 282-291.

Surfactants are commonly used to improve the stability of protein drug products; however, this stability is often insufficient. In this paper, the performance of FM1000, a surfactant containing an alkyl chain, an amino acid, and a polyether amine, is compared to Polysorbate 20, Polysorbate 80, and Poloxamer 188 in the presence of IgG and abatacept. First, surface tension measurements performed with an automatic drop tensiometer ( TRACKER™ by TECLIS) showed that FM1000 stabilizes an interface 1 to 2 orders of magnitude faster than the other probed surfactants. These results were confirmed by interfacial rheology experiments. These experimental data allowed to determine the surfactant diffusion to the interface using the Lucassen-van den Temple diffusion-exchange model. These results provide mechanistic understanding of the key causes and drivers of protein aggregation.

TECLIS product: TRACKER™ automatic drop tensiometer, automatic CMC

Key words: Surface tension, Interfacial dilatational rheology, protein-surfactant interactions, diffusion.

How to efficiently track fluorescent nanocarriers ? 

Reference: Bastiat, G.; Pritz, C. O.; Roider, C.; Fouchet, F.; Lignières, E.; Jesacher, A.; Glueckert, R.; Ritsch-Marte, M.; Schrott-Fischer, A.; Saulnier, P., A new tool to ensure the fluorescent dye labeling stability of nanocarriers: a real challenge for fluorescence imaging. Journal of controlled release 2013, 170 (3), 334-342.

Reading the interfacial activity gives information about the localization of molecules. When molecules reach the interface due to their amphiphilic properties, they lower the surface tension value. In  this paper, adsorption kinetics were obtained at a Labrafac-water interface. Organic dyes (NR, 6-Cou, DiI and DiD) were dissolved in the oil phase prior to measurements. Dynamic surface tension experiments show that NR and 6-Cou do not change the interfacial tension whereas Dil and Dio lower the interfacial tension suggesting that DiI and DiD dyes behave as amphiphilic molecules and move from the oily core of the drop to the Labrafac-water interface. Furthermore, it was demonstrated that dyes like NR and 6-Cou could be transferred from the LNCs (lipid nano-capsules) to an oily medium or can enter blank LNCs from oily compartment. In addition, no transfer of indocarbocyanine dyes occurred. These two antagonistic properties can be explained by different dye localizations inside the nanocarrier. NR and 6-Cou localized in the core of the LNCs could be transferred in the presence of an external lipophilic compartment whereas DiI, DiO and DiD, trapped in the shell of the LNCs, could not be transferred, even in the presence of an external lipophilic compartment.

TECLIS product: TRACKER™ automatic drop tensiometer

Key words: nanocarriers, migration, fluorescent dye, surface tension .

Can peptides bind to lipid nano-capsules and enhance their delivery ? 

Reference: Balzeau, J.; Pinier, M.; Berges, R.; Saulnier, P.; Benoit, J.-P.; Eyer, J., The effect of functionalizing lipid nanocapsules with NFL-TBS. 40-63 peptide on their uptake by glioblastoma cells. Biomaterials 2013, 34 (13), 3381-3389.

The aim of this study is to test whether a cell-penetrating peptide, NFL-TBS.40-63,  can increase the targeted uptake by glioblastoma cells of lipid nano-capsules filled with Paclitaxel, and thus increase their anti-proliferation in vitro and in vivo.  Surface tension measurements with an automatic drop tensiometer (TRACKER™ by TECLIS) at a Labrafac/water and Labrafac/water interface stabilized with Solutol were performed in a peptide range concentration from 0 to 14.10-5 mol/L. Results indicate that the peptide exhibits surfactant property at the oil/water interface but do not lower the surface tension in the presence of Solutol. Thus, this interfacial behavior suggests an

interaction with the Solutol and not directly with Labrafac. All these results demonstrate that the NFLTBS.40-63 peptide is adsorbed at the surfactant layer. Further characterizations with complementary techniques demonstrated that the NFL-TBS.40-63 peptide exhibits the ability to enhance the delivery of lipid nano-capsules in mouse glioma cells and astrocytes.

TECLIS product: TRACKER™ automatic drop tensiometer

Key words: drop tensiometry, surfactant-peptide interaction, drug delivery.

Can Eudragit RL100 stabilized Pickering nano-emulsions be used as a drug delivery system  ? 

Reference: Dieng, S. M., Omran, Z., Anton, N., Thioune, O., Djiboune, A. R., Sy, P. M., ... & Vandamme, T. (2020). Pickering nano-emulsions stabilized by Eudragit RL100 nanoparticles as oral drug delivery system for poorly soluble drugs. Colloids and Surfaces B: Biointerfaces, 191, 111010.

Pickering nano-emulsions are being investigated as drug delivery systems because they could offer many advantages: facilitate dermal drug delivery, increase the oral adsorption of poorly water-soluble drugs, etc. In this paper, the authors study Pickering nano-emulsions stabilized by Eudragit RL100 as drug delivery systems. Eudragit RL100 nano-particles (NPs) were chosen because they are stable towards the physiological conditions encountered in the gastro-intestinal tract and, as a model encapsulated drug, ketoprofen has been solubilized into the internal phase of the nano-emulsions. An important step of this study consisted in probing the interfacial properties of NPs in terms of surface tension and interfacial rheology using an automatic drop tensiometer (TRACKER™ by TECLIS). The experiments were performed at a C6H12 /aqueous NPs solution and showed that NPs adsorb at the interface and lower the interfacial tension. As for the interfacial rheology, the results showed that the oscillation frequency has an important impact on the conservative contribution E’. This interfacial behavior is very likely contributing to the observed stability of Eudragit RL100 stabilized Pickering nano-emulsions.

TECLIS product: TRACKER™ automatic drop tensiometer

Key words: Pickering nano-emulsions, interfacial tension, interfacial rheology.

Can fluorocarbon gas be used to generate nano-diamond-coated microbubbles for medical applications ? 

Reference: Mendoza-Ortega, E. E., Dubois, M., & Krafft, M. P. (2020). Fluorocarbon Gas Exposure Induces Disaggregation of Nanodiamond Clusters and Enhanced Adsorption, Enabling Medical Microbubble Formation. ACS Applied Nano Materials, 3(9), 8897-8905.

On the one hand, nano-diamonds (NDs) are intensively studied in biology and medicine for their potential application for sensing, bioimaging and drug delivery. However, their use is still limited due to their tendency to form aggregates. On the other hand, micro-bubbles (MBs), usually stabilized with a phospholipid shell, are used in medicine as ultrasound contrast agents. In this paper, the authors investigate the generation of MBs stabilized with a ND shell using fluorocarbon gas. Firstly, the disaggregating effect of fluorocarbon gases (F-hexane and F-pentane) on  ND25 (25nm in diameter) and their fluorinated analogs F-ND25 in aqueous solutions has been demonstrated. Secondly, the adsorption of NDs at water-gas interfaces is characterized with surface tension measurements using an automatic drop tensiometer (TRACKER™ by TECLIS). These results showed that ND25 adsorbs slowly and only slightly at an air/aqueous solution interface while exposing ND25 to F-hexane results in a faster and much pronounced adsorption. Similar results are reported for F-ND25 which indicates a synergetic effect between F-hexane and NDs at the interface. Finally, the authors show that fluorocarbon gas enables the production of microbubbles shelled only with nano-diamonds, in the absence of any other surfactant, which could not be achieved without the fluorocarbon being present.

TECLIS product: TRACKER™ automatic drop tensiometer

Key words: surface tension, nanoparticle, fluorocarbon gas, nano-diamond, micro-bubbles.