Synthesis of Polylactide‐Based Core–Shell Interface Cross‐Linked Micelles for Anticancer Drug Delivery

• Published in: Macromolecular bioscience Vol. 17; no. 3; pp. np - n/a
• Main Authors: Chen, Chih‐Kuang, Lin, Wei‐Jen, Hsia, Yu, Lo, Leu‐Wei
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.03.2017
• Subjects: Biodegradable materials; biodegradable polymers; Cell Line, Tumor; cross‐linked micelles; Cytotoxicity; Doxorubicin - administration & dosage; Doxorubicin - chemical synthesis; drug delivery; Drug Delivery Systems; Female; Humans; Micelles; nanocarriers; Physiology; Polyesters - administration & dosage; Polyesters - chemical synthesis; polylactide; Sarcoma - drug therapy; Sarcoma - pathology; Uterine Neoplasms - drug therapy; Uterine Neoplasms - pathology; drug delivery; polylactide; cross-linked micelles; biodegradable polymers; nanocarriers
• ISSN: 1616-5187; 1616-5195
• DOI: 10.1002/mabi.201600191

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. Core–shell interface cross‐linked micelles (ICMs) that possess enhanced in vivo stability, biodegradability, and negligible cytotoxicity are created via newly synthesized poly(ethylene glycol)‐b‐allyl functional polylatide‐b‐polylactides. Without burst release problems, Dox‐loaded ICMs are capable of exhibiting a slow and sustained Dox release feature at pH = 7.4. ICMs are successful in delivering Dox into human uterine sarcoma (MES‐SA) cells, followed by the inhibition of MES‐SA proliferation.