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Major effects on blood-retina barrier passage by minor alterations in design of polybutylcyanoacrylate nanoparticles

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Version 2 2020-02-17, 14:45
Version 1 2018-11-26, 10:48
journal contribution
posted on 2020-02-17, 14:45 authored by Qing You, Talea Hopf, Werner Hintz, Stefan Rannabauer, Nadine Voigt, B. van Wachem, Petra Henrich-Noack, Bernhard A. Sabel

Because the blood-brain barrier (BBB) is an obstacle for drug-delivery, carrier systems such as polybutylcyanoacrylate (PBCA) nanoparticles (NPs) have been studied. Yet, little is known of how physiochemical features such as size, surfactants and surface charge influence BBB passage in vivo. We now used a rat model of in vivo imaging of the retina - which is brain tissue and can reflect the situation at the BBB - to study how size and surface charge determine NPs’ ability to cross the blood-retina barrier (BRB). Interestingly, for poloxamer 188-modified, DEAE-dextran-stabilised, fluorescent PBCA NPs, decreasing the average zeta-size from 272 nm to 172 nm by centrifugation reduced the BRB passage of the NPs substantially. Varying the zeta potential within the narrow range of 0–15 mV by adding different amounts of stabiliser revealed that 0 mV and 15 mV were less desirable than 5 mV which facilitated the BRB passage. Moreover, whether the fluorescent marker was adsorbed or incorporated also influenced the transport into the retina tissue. Thus, minor changes in design of nano-carriers can alter physicochemical parameters such as size or zeta potential, thus substantially influencing NPs’ biological distribution in vivo, possibly by interactions with blood constituents and peripheral organs.

Funding

Our project “Nanoparticle Functionalization for Blood-Brain Barrier Passage” was funded by German Research Foundation [SA433/28–1]. Qing You was supported by China Scholarship Council [No. 201406370149]. Petra Henrich-Noack received funding from ERA.Net RUS PLUS [ID#169; NABUCO] coordinated by European Union and German Federal Ministry of Education and Research.

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