Fab’ enabled active targeting to steer delivery of poorly water-soluble drugs with HSA nanocapsules

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Abstract

In the present study, active targeting was achieved through the coupling of Fab’ fragments to a novel nanocapsule platform capable of encapsulating poorly water‑soluble drugs within an oily core. This approach aims to enable cell specificity while reducing immune recognition of the nanocapsules. Materials and Methods: The nanocapsules were prepared according to a previously published protocol with the model drug Lumogen Red® incorporated into a medium chain triglyceride core. Surface modification of the nanocapsules was carried out with PEGylation and following binding of a targeting agent. Two different targeting agents were used: trastuzumab and its Fab’ fragment. Either dialysis or SEC was used to separate unbound surface modification agents. Active targeting was analyzed with fluorescence microscopy of BT-474 cells, which overexpress the HER2 receptor (trastuzumab’s target). Immunogenicity of the nanocapsules was investigated by incubation with THP-1 monocytes and flow cytometry. Results and Discussion: The nanocapsules showed a narrowly distributed PDI. The hydrodynamic diameter increased from around 150 nm to 170 nm with surface modification and was stable for at least one month. Nanocapsules with no surface modification showed a low level of unspecific interaction which was inhibited by PEGylation. After coupling with either trastuzumab or Fab’ fragment the nanocapsules showed an increase in interaction for both targeting agents. Therefore, active targeting with the antibody and its fragment was successful. Incubation of the nanocapsules with THP-1 monocytes highlighted the moderation of the immune response by profoundly lowering the uptake of PEGylated and Fab’ coupled nanocapsules. Collectively, these findings demonstrate that Fab′ conjugation represents a viable approach to enable active targeting of nanocarriers while moderating their immunogenicity.

Speakers from the University of Münster

Kurze, Tobias Maximilian

Professorship of Pharmaceutical Technology and Biopharmacy (Prof. Langer)