Thermo-responsive drug delivery from polymeric micelles constructed using block copolymers of poly(N-isopropylacrylamide) and poly(butylmethacrylate)

• Published in: Journal of controlled release 1999-11, Vol.62 (1-2), p.115-127
• Main Authors: Chung, J.E, Yokoyama, M, Yamato, M, Aoyagi, T, Sakurai, Y, Okano, T
• Format: Article
• Language: English
• Subjects: Acrylic Resins; Animals; Antineoplastic agents; Biological and medical sciences; Cattle; Cell Survival - drug effects; Doxorubicin - administration & dosage; Drug delivery; Drug Delivery Systems; General aspects; General pharmacology; Medical sciences; Micelles; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Poly(butylmethacrylate); Poly(N-isopropylacrylamide); Polymeric micelle; Polymers; Polymethacrylic Acids; Temperature; Thermo-response
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/S0168-3659(99)00029-2

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°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.