Thermo-responsive drug delivery from polymeric micelles constructed using block copolymers of poly(N-isopropylacrylamide) and poly(butylmethacrylate).
To achieve a combination of spatial specificity in a passive manner with a stimuli-responsive targeting mechanism, a temperature-responsive polymeric micelle is prepared using block copolymers of (poly(N-isopropylacrylamide-b-butylmethacrylate) (PIPAAm-PBMA)). The micelle inner core formed by self-aggregates of PBMA segments successfully loaded with a drug (adriamycin), and the outer shell of PIPAAm chains played a role of stabilization and initiation of micellar thermo-response. Optimum conditions were investigated for the micelle formation and drug loading into the inner cores in a view of micellar stability and function as drug carriers. Outer shell hydrophilicity that prevents inner core interaction with biocomponents and other micelles can be suddenly switched to hydrophobic at a specific site by local temperature increase beyond the LCST (lower critical solution temperature) (32.5 degrees C). These micelles showed reversible structural changes allowing drug release upon heating/cooling thermal fluctuations through the LCST. Polymeric micelles incorporated with adriamycin showed a dramatic thermo-responsive on/off switching behavior for both drug release and in vitro cytotoxicity according to the temperature responsive structural changes of a micellar shell structure. The reversible and sensitive thermo-response of the micelle opens up opportunities to construct a novel drug delivery system in conjunction with localized hyperthermia.
Chung
J E
JE
Institute of Biomedical Engineering, Tokyo Women's Medical University, Kawada-cho 8-1, Shinjuku-ku, Tokyo, Japan.
Yokoyama
M
M
Yamato
M
M
Aoyagi
T
T
Sakurai
Y
Y
Okano
T
T
D000180:Acrylic Resins; D000818:Animals; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage; D016503:Drug Delivery Systems; D008823:Micelles; D011108:Polymers; D011109:Polymethacrylic Acids; D013696:Temperature
D000180:Acrylic Resins; D008823:Micelles; D011108:Polymers; D011109:Polymethacrylic Acids; C052970:poly-N-isopropylacrylamide; D004317:Doxorubicin; C068872:polybutyl methacrylate