Microneedle Patch Delivery of PROTACs for Anti-Cancer Therapy.

ABSTRACT: Proteolysis-targeting chimera (PROTAC) is an emerging technique for degrading disease-related proteins. However, the current PROTACs suffer from inadequate solubility and lack of organ targeting, which has hampered their druggability. Herein, we report direct and sustained delivery of PROTACs using microneedle patches to the diseased tissues. In this study, we use an estrogen receptor alpha (ERα)-degrading PROTAC, ERD308, to treat ER-positive breast cancer. A pH-sensitive micelle, MPEG-poly(β-amino ester) (MPEG-PAE), is used to encapsulate ERD308 along with an FDA-approved CDK4/6 inhibitor, Palbociclib (Pal), before loading into biodegradable microneedle patches. These patches enable prolonged drug release into deep tumors, maintaining therapeutic levels for at least 4 days, with an excell

SUBMITTER: Cheng X 

PROVIDER: S-EPMC11393661 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature