Systematic evaluation of design features enables efficient selection of Π electron-stabilized polymeric micelles

Maryam Sheybanifard, Nataliia Beztsinna, Mahsa Bagheri, Eva Miriam Buhl, Jaleesa Bresseleers, Aida Varela-Moreira, Yang Shi, Cornelus F van Nostrum, Gabri van der Pluijm, Gert Storm, Wim E Hennink, Twan Lammers, J.M. Metselaar (Corresponding author)

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2 Citations (Scopus)

Abstract

Polymeric micelles (PM) based on poly(ethylene glycol)-b-poly(N-2-benzoyloxypropyl methacrylamide) (mPEG-b-p(HPMA-Bz)) loaded with paclitaxel (PTX-PM) have shown promising results in overcoming the suboptimal efficacy/toxicity profile of paclitaxel. To get insight into the stability of PTX-PM formulations upon storage and to optimize their in vivo tumor-targeted drug delivery properties, we set out to identify a lead PTX-PM formulation with the optimal polymer composition. To this end, PM based on four different mPEG5k-b-p(HPMA-Bz) block copolymers with varying molecular weight of the hydrophobic block (17–3 kDa) were loaded with different amounts of PTX. The hydrodynamic diameter was 52 ± 1 nm for PM prepared using polymers with longer hydrophobic blocks (mPEG5k-b-p(HPMA-Bz)17k and mPEG5k-b-p(HPMA-Bz)10k) and 39 ± 1 nm for PM composed of polymers with shorter hydrophobic blocks (mPEG5k-b-p(HPMA-Bz)5k and mPEG5k-b-p(HPMA-Bz)3k). The best storage stability and the slowest PTX release was observed for PM with larger hydrophobic blocks. On the other hand, smaller sized PM of shorter mPEG5k-b-p(HPMA-Bz)5k showed a better tumor penetration in 3D spheroids. Considering better drug retention capacity of the mPEG5k-b-p(HPMA-Bz)17k and smaller size of the mPEG5k-b-p(HPMA-Bz)5k as two desirable design features, we argue that PM based on these two polymers are the lead candidates for further in vivo studies.
Original languageEnglish
Article number119409
Number of pages10
JournalInternational Journal of Pharmaceutics
Volume584
DOIs
Publication statusPublished - 30 Jun 2020

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    Sheybanifard, M., Beztsinna, N., Bagheri, M., Buhl, E. M., Bresseleers, J., Varela-Moreira, A., Shi, Y., van Nostrum, C. F., van der Pluijm, G., Storm, G., Hennink, W. E., Lammers, T., & Metselaar, J. M. (2020). Systematic evaluation of design features enables efficient selection of Π electron-stabilized polymeric micelles. International Journal of Pharmaceutics, 584, [119409]. https://doi.org/10.1016/j.ijpharm.2020.119409