title: Rapid liposome quality assessment using a lab-on-a-chip.
abstract: Although liposomes have many outstanding features such as biocompatibility, biodegradability, low toxicity and structural diversity, and are successfully applied in many areas of chemistry and biotechnology, a lack of characterization standards and quality control tools are still inhibiting the translation of liposome technology into clinical routine. The greatest obstacle to clinical scale commercialization is the inability to ensure liposome formulation stability because small size variations or altered surface chemistries can significantly influence in vivo distribution and excretion kinetics that could in turn lead to unpredictable therapy outcomes. To enhance the product development process we have developed a microfluidic biochip containing embedded dielectric microsensors capable of providing quantitative results on formulation composition and stability based on the monitoring of the unique electric properties of liposomes. Computational fluid dynamic (CFD) simulations confirmed that microfluidics offer reproducible and well-defined measurement conditions where a moving liposome suspension within a microchannel behaves like a bulk material. Results of this study demonstrate the ability of microfluidics, in combination with dielectric spectroscopy and multivariate data analysis methods, to identify nine different liposomes. We also show that various liposome modifications such as membrane-bound surface proteins, lipid bilayer soluble drugs, as well as protein and dye encapsulations, can be detected in the absence of any labels or indicators. Since shelf-life stability of a liposome formulation is regarded of prime importance for regulatory approval and clinical application, we further provide a possible practical application of the developed liposome analysis platform as a high-throughput tool for industrial quality insurance purposes.
authors.affiliation: Department of Health & Environment, Nano Systems, AIT Austrian Institute of Technology, Donau-City Street 1, 1220 Vienna, Austria.
authors.forename: Gerald
authors.initials: G
authors.lastname: Birnbaumer
authors.forename: Seta
authors.initials: S
authors.lastname: Küpcü
authors.forename: Christian
authors.initials: C
authors.lastname: Jungreuthmayer
authors.forename: Lukas
authors.initials: L
authors.lastname: Richter
authors.forename: Karola
authors.initials: K
authors.lastname: Vorauer-Uhl
authors.forename: Andreas
authors.initials: A
authors.lastname: Wagner
authors.forename: Claudia
authors.initials: C
authors.lastname: Valenta
authors.forename: Uwe
authors.initials: U
authors.lastname: Sleytr
authors.forename: Peter
authors.initials: P
authors.lastname: Ertl
mesh_terms: D007090:Image Interpretation, Computer-Assisted; D007700:Kinetics; D056656:Lab-On-A-Chip Devices; D008081:Liposomes / Q000032:analysis*; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation / Q000379:methods*; D015999:Multivariate Analysis; D013499:Surface Properties
chemical_list: D008081:Liposomes