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Thermosensitive Liposomes for the Delivery of Gemcitabine and Oxaliplatin to Tumors
journal contribution
posted on 2013-12-02, 00:00 authored by Jonathan
P. May, Mark J. Ernsting, Elijus Undzys, Shyh-Dar LiThe
majority of ultrafast temperature sensitive liposome (uTSL)
formulations reported in the literature deliver the highly membrane
permeable drug, doxorubicin (DOX). Here we report on the study of
the uTSL formulation, HaT (Heat activated
cytoToxic, composed of the phospholipid DPPC and the
surfactant Brij78) loaded with the water-soluble, but poorly membrane
permeable anticancer drugs, gemcitabine (GEM) and oxaliplatin (OXA).
The HaT formulation displayed ultrafast release of these drugs in
response to temperature, whereas attempts with LTSL (Lyso-lipid Temperature Sensitive Liposome, composed of DPPC, MSPC, and DSPE-PEG) were unsuccessful.
HaT-GEM and HaT-OXA both released >80% of the encapsulated drug
within
2 min at 40–42 °C, with <5% drug leakage at 37 °C
after 30 min in serum. The pharmacokinetic profile of both drugs was
improved by formulating with HaT relative to the free drug, with clearance
reduced by 50-fold for GEM and 3-fold for OXA. HaT-GEM and HaT-OXA
both displayed improved drug uptake in the heated tumor relative to
the unheated tumor (by 9-fold and 3-fold, respectively). In particular,
HaT-GEM showed 25-fold improved delivery to the heated tumor relative
to free GEM and significantly enhanced antitumor efficacy with complete
tumor regression after a single dose of HaT-GEM. These data suggest
that uTSL technology can also be used to deliver nonmembrane permeable
drugs via an intravascular ultrafast release mechanism to great effect.
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Keywords
uTSL technologyTumorsThe majorityThermosensitive Liposomesultrafast temperatureencapsulated drugpharmacokinetic profileGEMLTSLOXAultrafast releaseDOXdrug uptake2 minanticancer drugstumor regressionphospholipid DPPCantitumor efficacyHaT formulationuTSL formulationintravascular ultrafast release mechanism30 minMSPC
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