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Near-Infrared Image-Guided Delivery and Controlled Release Using Optimized Thermosensitive Liposomes

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ABSTRACT

Purpose

To engineer optimized near-infrared (NIR) active thermosensitive liposomes to potentially achieve image-guided delivery of chemotherapeutic agents.

Methods

Thermosensitive liposomes were surface-coated with either polyethylene glycol or dextran. Differential scanning calorimetry and calcein release studies were conducted to optimize liposomal release, and flow cytometry was employed to determine the in vitro macrophage uptake of liposomes. Indocyanine green (ICG) was encapsulated as the NIR dye to evaluate the in vivo biodistribution in tumor-bearing mice.

Results

The optimized thermosensitive liposome formulation consists of DPPC, SoyPC, and cholesterol in the 100:50:30 molar ratio. Liposomes with dextran and polyethylene glycol demonstrated similar thermal release properties; however in vitro macrophage uptake was greater with dextran. Non-invasive in vivo NIR imaging showed tumor accumulation of liposomes with both coatings, and ex vivo NIR imaging correlated well with actual ICG concentrations in various organs of healthy mice.

Conclusions

The optimized thermosensitive liposome formulation demonstrated stability at 37 °C and efficient burst release at 40 and 42 °C. Dextran exhibited potential for application as a surface coating in thermosensitive liposome formulations. In vivo studies suggest that liposomal encapsulation of ICG permits reliable, real-time monitoring of liposome biodistribution through non-invasive NIR imaging.

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Abbreviations

DEX:

dextran

DPPC:

dipalmitoylphosphatidylcholine

DSPE:

distearoylphosphatidylethanolamine

ICG:

indocyanine green

MPPC:

monopalmitoylphosphatidylcholine

NIR:

near-infrared

PEG:

polyethylene glycol

RES:

reticuloendothelial system

Soy-PC:

soy-phosphatidylcholine

Tm :

transition temperature

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ACKNOWLEDGMENTS & DISCLOSURES

This work was supported by Mercer University Seed Grant and Georgia Cancer Coalition Cancer Research Award. D. C. Turner and D. Moshkelani received Pre-Doctoral fellowships from the American Foundation of Pharmaceutical Education. Some experiments were conducted in the Chemistry Department of Emory University.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Mercer University, Atlanta, Georgia, 30341, USA

    David C. Turner, Delaram Moshkelani, Colby S. Shemesh, David Luc & Hailing Zhang

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  1. David C. Turner
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  2. Delaram Moshkelani
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Correspondence to Hailing Zhang.

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Turner, D.C., Moshkelani, D., Shemesh, C.S. et al. Near-Infrared Image-Guided Delivery and Controlled Release Using Optimized Thermosensitive Liposomes. Pharm Res 29, 2092–2103 (2012). https://doi.org/10.1007/s11095-012-0738-0

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  • DOI: https://doi.org/10.1007/s11095-012-0738-0

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