TY - JOUR
T1 - Systematic evaluation of design features enables efficient selection of Π electron-stabilized polymeric micelles
AU - Sheybanifard, Maryam
AU - Beztsinna, Nataliia
AU - Bagheri, Mahsa
AU - Buhl, Eva Miriam
AU - Bresseleers, Jaleesa
AU - Varela-Moreira, Aida
AU - Shi, Yang
AU - van Nostrum, Cornelus F.
AU - van der Pluijm, Gabri
AU - Storm, Gert
AU - Hennink, Wim E.
AU - Lammers, Twan
AU - Metselaar, Josbert M.
PY - 2020/6/30
Y1 - 2020/6/30
N2 - 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.
AB - 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.
KW - 3D cell culture
KW - In vitro release kinetics
KW - Paclitaxel
KW - Polymeric micelles
KW - Storage stability
KW - π-π stacking interactions
KW - 22/2 OA procedure
UR - http://www.scopus.com/inward/record.url?scp=85085284229&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2020.119409
DO - 10.1016/j.ijpharm.2020.119409
M3 - Article
C2 - 32389790
AN - SCOPUS:85085284229
SN - 0378-5173
VL - 584
JO - International journal of pharmaceutics
JF - International journal of pharmaceutics
M1 - 119409
ER -