Localized delivery of doxorubicin in vivo from polymer-modified thermosensitive liposomes with MR-guided focused ultrasound-mediated heating

JOURNAL OF CONTROLLED RELEASE

卷:194

Article

Ta, Terence¹  Bartolak-Suki, Elizabeth¹  Park, Eun-Joo²  Karrobi, Kavon¹  McDannold, Nathan J.²  Porter, Tyrone M.³ 

[1] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA

[2] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA

[3] Boston Univ, Dept Mech Engn, Boston, MA 02215 USA

关键词: Drug delivery;    Thermosensitive liposomes;    Smart polymers;    MR-guided focused ultrasound;    NIPAAm;    Chemotherapy;   

DOI  :  10.1016/j.jconrel.2014.08.013

来源: Elsevier

【 摘 要 】

Thermosensitive liposomes have emerged as a viable strategy for localized delivery and triggered release of chemotherapy. MR-guided focused ultrasound (MRgFUS) has the capability of heating tumors in a controlled manner, and when combined with thermosensitive liposomes can potentially reduce tumor burden in vivo. However, the impact of this drug delivery strategy has rarely been investigated. We have developed a unique liposome formulation modified with p(NIPAAm-co-PAA), a polymer that confers sensitivity to both temperature and pH. These polymer-modified thermosensitive liposomes (PTSL) demonstrated sensitivity to focused ultrasound, and required lower thermal doses and were more cytotoxic than traditional formulations in vitro. A set of acoustic parameters characterizing optimal release from PTSL in vitro was applied in the design of a combined MRgFUS/PTSL delivery platform. This platform more effectively reduced tumor burden in vivo when compared to free drug and traditional formulations. Histological analysis indicated greater tumor penetration, more extensive ECM remodeling, and greater cell destruction in tumors administered PTSL, correlating with improved response to the therapy. (C) 2014 Elsevier B.V. All rights reserved.

【 授权许可】

Free