Cargo–carrier interactions significantly contribute to micellar conformation and biodistribution

• Published in: NPG Asia materials Vol. 9; no. 10; p. e444
• Main Authors: Press, Adrian T, Ramoji, Anuradha, vd Lühe, Moritz, Rinkenauer, Alexandra C, Hoff, Jessica, Butans, Marianne, Rössel, Carsten, Pietsch, Christian, Neugebauer, Ute, Schacher, Felix H, Bauer, Michael
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.10.2017; Nature Publishing Group
• Subjects: 639/301/357/354; 639/301/357/537; 639/638/298/54/152; 639/638/92/436/1729; Biodistribution; Biomaterials; Cargo; Chemical properties; Drug delivery systems; Drugs; Encapsulation; Energy Systems; Localization; Materials Science; Micelles; Optical and Electronic Materials; Organelles; original-article; Pharmacology; Polymers; Risk assessment; Self-assembly; Structural Materials; Surface and Interface Science; Terpolymers; Thin Films
• ISSN: 1884-4049; 1884-4057
• DOI: 10.1038/am.2017.161

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. On the basis of previous work, a versatile class of nanocarriers is 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 as differences in cargo location occur. Thus, these interactions have to be considered when a carrier system is selected to achieve optimal delivery to a given tissue. Nanomedicine: Interactions between drugs and carriers affect delivery Molecular cargos and encapsulation conditions can affect the effectiveness of polymer micelles for targeted drug delivery. Made from long chains bearing both hydrophobic and hydrophilic units, polymer micelles trap drugs in self-assembled spheres of diameters below 50 nanometers – a critical diameter to reach cells and their organelles within complex tissues. Michael Bauer, Felix Schacher and their teams from University Hospital and Friedrich Schiller University, Jena (Germany) have now demonstrated that the interplay of cargo structure and encapsulation conditions affect cargo localization and the timing of release. Among other methods, they used Raman imaging to observe how the polymers encapsulated and released two different model dyes. Net micellar charge and the system's pH influenced where the drugs are localized within the polymer micelles – differences that manifested as variable accumulation in (sub)cellular niches in live animal studies. Physico-chemical properties of the cargo as well as the actual conditions during encapsulation interfere during formulation of nanoparticular cargo–carrier systems. We demonstrate altered chain conformations in the different micelles due to different cargo–carrier interactions leading to different localization of model drugs within the carrier. Finally, these changes lead to differences in pharmacokinetics and biodistribution in vivo , showing the relevance of such effects in a translational manner.