TY - JOUR
T1 - Tethered polymer nanoassemblies for sustained carfilzomib release and prolonged suppression of proteasome activity
AU - Reichel, Derek
AU - Lee, Min Jae
AU - Lee, Wooin
AU - Kim, Kyung Bo
AU - Bae, Younsoo
N1 - Publisher Copyright:
© 2016 Future Science Ltd.
PY - 2016/10
Y1 - 2016/10
N2 - Aim: Proteasome inhibitors, such as carfilzomib (CFZ), have shown potential to treat various types of cancers in preclinical models, but clinical applications are limited likely due to formulation and delivery issues. Results & methodology: Tethered polymer nanoassemblies (TNAs) were synthesized by tethering hydrophilic polymers and hydrophobic groups to charged polymer scaffolds, and then end-capping remaining amines on scaffold. Drug entrapment and drug release half-lives increased as charge was removed from scaffold. TNAs with sustained CFZ release maintained drug efficacy after preincubation and increased duration of proteasome inhibition in cancer cells compared with free CFZ. Conclusion: TNAs fine-tuned CFZ release as charge was removed from polymer scaffold, which allowed for sustained proteasome inhibition in cancer cells and potentially enhanced anticancer efficacy.
AB - Aim: Proteasome inhibitors, such as carfilzomib (CFZ), have shown potential to treat various types of cancers in preclinical models, but clinical applications are limited likely due to formulation and delivery issues. Results & methodology: Tethered polymer nanoassemblies (TNAs) were synthesized by tethering hydrophilic polymers and hydrophobic groups to charged polymer scaffolds, and then end-capping remaining amines on scaffold. Drug entrapment and drug release half-lives increased as charge was removed from scaffold. TNAs with sustained CFZ release maintained drug efficacy after preincubation and increased duration of proteasome inhibition in cancer cells compared with free CFZ. Conclusion: TNAs fine-tuned CFZ release as charge was removed from polymer scaffold, which allowed for sustained proteasome inhibition in cancer cells and potentially enhanced anticancer efficacy.
KW - cancer chemotherapy
KW - controlled release
KW - nanoparticles
KW - proteasome inhibitors
KW - solid cancers
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U2 - 10.4155/tde-2016-0041
DO - 10.4155/tde-2016-0041
M3 - Article
C2 - 27790952
AN - SCOPUS:84994112541
SN - 2041-5990
VL - 7
SP - 665
EP - 681
JO - Therapeutic Delivery
JF - Therapeutic Delivery
IS - 10
ER -