Localized delivery of doxorubicin in vivo from polymer-modified thermosensitive liposomes with MR-guided focused ultrasound-mediated heating
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 b...
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| Veröffentlicht in: | Journal of controlled release 2014-11, Vol.194, p.71-81 |
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| container_title | Journal of controlled release |
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| creator | Ta, Terence Bartolak-Suki, Elizabeth Park, Eun-Joo Karrobi, Kavon McDannold, Nathan J. Porter, Tyrone M. |
| description | 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.
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| doi_str_mv | 10.1016/j.jconrel.2014.08.013 |
| format | Article |
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[Display omitted]</description><subject>Acrylamides</subject><subject>Animals</subject><subject>Antibiotics, Antineoplastic - administration & dosage</subject><subject>Antibiotics, Antineoplastic - pharmacokinetics</subject><subject>Antibiotics, Antineoplastic - pharmacology</subject><subject>Cell Survival - drug effects</subject><subject>Chemotherapy</subject><subject>Doxorubicin - administration & dosage</subject><subject>Doxorubicin - pharmacokinetics</subject><subject>Doxorubicin - pharmacology</subject><subject>Drug delivery</subject><subject>Drug Delivery Systems</subject><subject>Excipients</subject><subject>Hot Temperature</subject><subject>Humans</subject><subject>Hydrogen-Ion Concentration</subject><subject>Liposomes - chemistry</subject><subject>Magnetic Resonance Spectroscopy</subject><subject>MCF-7 Cells</subject><subject>MR-guided focused ultrasound</subject><subject>Neoplasms, Experimental - drug therapy</subject><subject>Neoplasms, Experimental - pathology</subject><subject>NIPAAm</subject><subject>Particle Size</subject><subject>Polymers</subject><subject>Rats</subject><subject>Rats, Inbred F344</subject><subject>Smart polymers</subject><subject>Temperature</subject><subject>Thermosensitive liposomes</subject><subject>Ultrasonics</subject><issn>0168-3659</issn><issn>1873-4995</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkd-q1DAQxosonvXoIyi99KY1aZq0vVHk4D9YEUSvQ5tMdmdJO2vSVtdn8KHNYdeDXgmBgczvm_mYL8ueclZyxtWLQ3kwNAXwZcV4XbK2ZFzcyza8bURRd528n20S1xZCye4qexTjgTEmRd08zK4qySXv2mqT_dqS6T3-BJtb8LhCOOXkcks_KCwDGpzy9FZcKXeBxvxI_jRCKEay6DCp5j2EkSJMEeckzz0eKdIIMf-O8z7_-LnYLWgT6MgsMdXFz6GPtEy2GMFiP6e_PfQzTrvH2QPX-whPLvU6-_r2zZeb98X207sPN6-3hZGMzYWEqlGqEUYOrpNWKKWEk9IIVg9cqsrUtq8a2xkFQw22ZaqR1dA4oRrgxglxnb08zz0uQ_JgYEqWvD4GHPtw0tSj_rcz4V7vaNV1JWtWsTTg-WVAoG8LxFmPGA14309AS9RcCckEV0wlVJ5REyjGAO5uDWf6Nkl90Jck9W2SmrU6JZl0z_72eKf6E10CXp0BSJdaEYKOBmEy6aYBzKwt4X9W_AbWzLd0</recordid><startdate>20141128</startdate><enddate>20141128</enddate><creator>Ta, Terence</creator><creator>Bartolak-Suki, Elizabeth</creator><creator>Park, Eun-Joo</creator><creator>Karrobi, Kavon</creator><creator>McDannold, Nathan J.</creator><creator>Porter, Tyrone M.</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-8382-8860</orcidid></search><sort><creationdate>20141128</creationdate><title>Localized delivery of doxorubicin in vivo from polymer-modified thermosensitive liposomes with MR-guided focused ultrasound-mediated heating</title><author>Ta, Terence ; 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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.
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| issn | 0168-3659 1873-4995 |
| language | eng |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Acrylamides Animals Antibiotics, Antineoplastic - administration & dosage Antibiotics, Antineoplastic - pharmacokinetics Antibiotics, Antineoplastic - pharmacology Cell Survival - drug effects Chemotherapy Doxorubicin - administration & dosage Doxorubicin - pharmacokinetics Doxorubicin - pharmacology Drug delivery Drug Delivery Systems Excipients Hot Temperature Humans Hydrogen-Ion Concentration Liposomes - chemistry Magnetic Resonance Spectroscopy MCF-7 Cells MR-guided focused ultrasound Neoplasms, Experimental - drug therapy Neoplasms, Experimental - pathology NIPAAm Particle Size Polymers Rats Rats, Inbred F344 Smart polymers Temperature Thermosensitive liposomes Ultrasonics |
| title | Localized delivery of doxorubicin in vivo from polymer-modified thermosensitive liposomes with MR-guided focused ultrasound-mediated heating |
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