Journal
JOURNAL OF CONTROLLED RELEASE
Volume 194, Issue -, Pages 71-81Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2014.08.013
Keywords
Drug delivery; Thermosensitive liposomes; Smart polymers; MR-guided focused ultrasound; NIPAAm; Chemotherapy
Funding
- NCI NIH HHS [R25 CA153955] Funding Source: Medline
- NIGMS NIH HHS [T32 GM008541] Funding Source: Medline
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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.
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