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Cargo-carrier-interactions significantly contribute to micellar conformation and biodistribution

Press, Adrian T.; Ramoji, Anuradha A.; von der Lühe, Moritz; Rinkenauer, Alexandra C.; Hoff, Jessica; Butans, Marianne; Rössel, Carsten; Pietsch, Christian; Neugebauer, Ute; Schacher, Felix H.; Bauer, Michael
in: NPG Asia Materials (2017) e444-1

Strategies to deliver drugs using nanocarriers, which are passively or actively targeted to their alleged site of action might favorably affect benefit-risk-profiles of novel therapeutics. Here, we tested the hypothesis whether the physico-chemical properties of the cargo as well as the actual conditions during encapsulation interfere during formulation of nanoparticular cargo-carrier systems. Based on previous work, a versatile class of nanocarriers are polyether-based ABC triblock terpolymer micelles with diameters below 50 nm. Their tunable chemistry and size allows to systematically vary important parameters. We demonstrate in vivo differences in pharmacokinetics and biodistribution not only dependent on micellar net charge but also on the properties of encapsulated (model) drugs and their localization within the micelles. On the basis of in vitro and in vivo evidence we propose that depending on drug cargo and encapsulation conditions micelles with homogeneous or heterogeneous corona structure are formed, contributing to an altered pharmacokinetic profile. Thus, these interactions have to be considered when a carrier system is selected to achieve optimal delivery to a given tissue.

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