Skip to Content
Merck
  • Localized delivery of doxorubicin in vivo from polymer-modified thermosensitive liposomes with MR-guided focused ultrasound-mediated heating.

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

Journal of controlled release : official journal of the Controlled Release Society (2014-08-26)
Terence Ta, Elizabeth Bartolak-Suki, Eun-Joo Park, Kavon Karrobi, Nathan J McDannold, Tyrone M Porter
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
L-Glutamine
Supelco
L-Glutamine, certified reference material, TraceCERT®, Manufactured by: Sigma-Aldrich Production GmbH, Switzerland
SAFC
L-Glutamine
Sigma-Aldrich
L-Glutamine, γ-irradiated, BioXtra, suitable for cell culture
Sigma-Aldrich
L-Glutamine, meets USP testing specifications, suitable for cell culture, 99.0-101.0%, from non-animal source
Sigma-Aldrich
L-Glutamine, BioUltra, ≥99.5% (NT)
Sigma-Aldrich
L-Glutamine, ReagentPlus®, ≥99% (HPLC)
Supelco
Residual Solvent - Chloroform, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
HEPES buffer solution, 1 M in H2O
Sigma-Aldrich
1,2-Dipalmitoyl-sn-glycero-3-phosphocholine, ≥99% (TLC)
Sigma-Aldrich
1,2-Dipalmitoyl-sn-glycero-3-phosphocholine, semisynthetic, ≥99%
Supelco
L-Glutamine, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
2-Propylacrylic acid, 99%
SAFC
Cholesterol, Plant-Derived, SyntheChol®
SAFC
HEPES
Sigma-Aldrich
N-Isopropylacrylamide, ≥99%
Sigma-Aldrich
SyntheChol® NS0 Supplement, 500 ×, synthetic cholesterol, animal component-free, aqueous solution, sterile-filtered, suitable for cell culture
Sigma-Aldrich
2-(Dodecylthiocarbonothioylthio)-2-methylpropionic acid, 98% (HPLC)
Doxorubicin hydrochloride, European Pharmacopoeia (EP) Reference Standard
SAFC
HEPES
SAFC
Cholesterol, from sheep wool, Controlled origin, meets USP/NF testing specifications
Sigma-Aldrich
Cholesterol, from lanolin, ≥99.0% (GC)
Sigma-Aldrich
Cholesterol, tested according to Ph. Eur.
Sigma-Aldrich
Cholesterol, Sigma Grade, ≥99%
Sigma-Aldrich
Cholesterol, powder, BioReagent, suitable for cell culture, ≥99%
Sigma-Aldrich
Chloroform, anhydrous, ≥99%, contains 0.5-1.0% ethanol as stabilizer
Supelco
Cholesterol solution, certified reference material, 10 mg/mL in chloroform
Sigma-Aldrich
Chloroform, HPLC Plus, for HPLC, GC, and residue analysis, ≥99.9%, contains amylenes as stabilizer
Sigma-Aldrich
Chloroform, contains ethanol as stabilizer, ACS reagent, ≥99.8%
Sigma-Aldrich
N-Isopropylacrylamide, 97%