Pentaglycine lipid derivates – rp-HPLC analytics for bioorthogonal anchor molecules in targeted, multiple-composite liposomal drug delivery systems

[Display omitted] The quantification of lipids and assessment of lipid composition is an indispensable step during the pharmaceutical development of novel lipid based drug delivery systems such as liposomes. Broad excipient screenings of such formulations raise the need for versatile analytical meth...

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Bibliographic Details
Published in:International journal of pharmaceutics 2018-08, Vol.547 (1-2), p.602-610
Main Authors: Wöll, Steffen, Schiller, Stefan, Bachran, Christopher, Swee, Lee Kim, Scherließ, Regina
Format: Article
Language:English
Subjects:
Bioconjugation
Evaporative light scattering
Lipid quantification
Liposomes
Sortase-A
Targeted drug delivery
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Summary:[Display omitted] The quantification of lipids and assessment of lipid composition is an indispensable step during the pharmaceutical development of novel lipid based drug delivery systems such as liposomes. Broad excipient screenings of such formulations raise the need for versatile analytical methods. Even more demanding complexity is generated by introduction of targeted systems requiring functionalized lipids. We addressed this demand by developing an rp-HPLC based analytical method with evaporative light scattering detection (ELSD) for the simultaneous analysis of commonly used phosphatidylcholines, cholesterol and bilayer surface-modifying cationic, anionic or PEGylated lipids, which can be analyzed in combination with novel pentaglycine lipids suitable as targeting ligand anchor. The method was validated for specificity, precision, accuracy and sample stability. We monitor the continuous and scalable manufacturing of two pentaglycine-modified liposomal formulations and track the modification of these drug delivery systems with a single-domain antibody utilizing bioorthogonal Sortase-A technology. Both the presented analytical and preparative techniques can help to improve the quality control and to accelerate the pharmaceutical development of such targeted drug delivery systems.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2018.05.052