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K. Wieland, V. Weiss, G. Ramer, A. Centrone, G. Allmaier, B. Lendl:
"Accessing drug encapsulation in liposomal nanocarriers with nanoscale lateral resolution through hyphenation of nES-GEMMA and PTIR spectroscopy";
Vortrag: SciX 2018, Atlanta, Georgia, USA (eingeladen); 21.10.2018 - 26.10.2018.

Unilamellar liposomes are spherical structures with a diameter ranging from double-digit to several hundred nanometers. Because of their structural and functional versatility in combination with biocompatibility and biodegradability, they are of great interest in medicine where they are employed as nanocarriers to transport anti-cancer drugs, anesthetics, anti-inflammatory drugs and other therapeutics. The main advantage compared to free drug administration is the increased stability of the drug once it is encapsulated and protected by the liposome´s lipid bilayer. Furthermore, the outer sphere of the liposome can be functionalized by a number of ligands to allow targeted transport to the diseased tissue/cell which in turn reduces toxic side effects because damage to healthy tissue/cell can be effectively lessened. This is especially important for chemotherapeutic drugs which are known for their toxicity and require careful drug dosage. Several analytical methods are available to determine the concentration of the encapsulated drug in bulk measurements such as capillary electrophoresis (CE) or high-pressure liquid chromatography (HPLC). However, in addition to a great batch to batch variation in drug encapsulation efficiency (EE) there is also a variation of up to 50% around the average EE-value within one liposome batch to be expected. Therefore, there is an urgent need for the development of new analytical approaches to determine drug load in single liposomes. Based on this knowledge, formulations and protocols for liposome preparation could be improved to obtain liposomes with a more consistent drug encapsulation efficiency and ultimately maximize the therapy efficacy while minimizing toxic side effects.
Here, we leverage the photothermal induced resonance technique -a combination of atomic force microscopy (AFM) with Infrared spectroscopy - to access label-free, molecule-specific information with nanoscale lateral resolution. The hyphenation of nES-GEMMA (nano-electrospray gas-phase electrophoretic mobility molecular analysis) and PTIR enables us to collect size-selected (roughly 80 nm in surface dry diameter), isolated and intact liposomes on a substrate for subsequent spectroscopic analysis. By leveraging a novel tapping-mode PTIR operation based on heterodyne detection, the force exerted by the AFM tip onto the nano-objects is reduced considerably making chemical imaging of the drug distribution inside the very soft liposomes possible for the first time.

PTIR, AFM-IR, nES GEMMA, liposomes, drug delivery