Synthesis of Polylactide-Based Core-Shell Interface Cross-Linked Micelles for Anticancer Drug Delivery.
Well-defined poly(ethylene glycol)-b-allyl functional polylactide-b-polylactides (PEG-APLA-PLAs) are synthesized through sequential ring-opening polymerization. PEG-APLA-PLAs that have amphiphilic properties and reactive allyl side chains on their intermediate blocks are successfully transferred to core-shell interface cross-linked micelles (ICMs) by micellization and UV-initiated irradiation. ICMs have demonstrated enhanced colloidal stability in physiological-mimicking media. Hydrophobic molecules such as Nile Red or doxorubicin (Dox) are readily loaded into ICMs; the resulting drug-ICM formulations possess slow and sustained drug release profiles under physiological-mimicking conditions. ICMs exhibit negligible cytotoxicity in human uterine sarcoma cancer cells by using biodegradable aliphatic polyester as the hydrophobic segments. Relative to free Dox, Dox-loaded ICMs show a reduced cytotoxicity due to the late intracellular release of Dox from ICMs. Overall, ICMs represent a new type of biodegradable cross-linked micelle and can be employed as a promising platform for delivering a broad variety of hydrophobic drugs.
Polymeric Biomaterial Laboratory, Department of Fiber and Composite Materials, Feng Chia University, Taichung, 40724, Taiwan.
Chih-Kuang
CK
Chen
Polymeric Biomaterial Laboratory, Department of Fiber and Composite Materials, Feng Chia University, Taichung, 40724, Taiwan.
Wei-Jen
WJ
Lin
Institute of Biotechnology, National Tsing Hua University, Hsinchu, 30013, Taiwan.|Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan, 35053, Taiwan.
Yu
Y
Hsia
Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan, 35053, Taiwan.
Leu-Wei
LW
Lo
D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage* / Q000138:chemical synthesis; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D008823:Micelles; D011091:Polyesters / Q000008:administration & dosage* / Q000138:chemical synthesis; D012509:Sarcoma / Q000188:drug therapy / Q000473:pathology; D014594:Uterine Neoplasms / Q000188:drug therapy / Q000473:pathology
D008823:Micelles; D011091:Polyesters; C033616:poly(lactide); D004317:Doxorubicin
biodegradable polymers; cross-linked micelles; drug delivery; nanocarriers; polylactide