An in vitro assessment of liposomal topotecan simulating metronomic chemotherapy in combination with radiation in tumor-endothelial spheroids View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-12

AUTHORS

Amar Jyoti, Kyle D Fugit, Pallavi Sethi, Ronald C McGarry, Bradley D Anderson, Meenakshi Upreti

ABSTRACT

Low dose metronomic chemotherapy (LDMC) refers to prolonged administration of low dose chemotherapy designed to minimize toxicity and target the tumor endothelium, causing tumor growth inhibition. Topotecan (TPT) when administered at its maximum tolerated dose (MTD) is often associated with systemic hematological toxicities. Liposomal encapsulation of TPT enhances efficacy by shielding it from systemic clearance, allowing greater uptake and extended tissue exposure in tumors. Extended release of TPT from liposomal formulations also has the potential to mimic metronomic therapies with fewer treatments. Here we investigate potential toxicities of equivalent doses of free and actively loaded liposomal TPT (LTPT) and compare them to a fractionated low dose regimen of free TPT in tumor-endothelial spheroids (TES) with/without radiation exposure for a prolonged period of 10 days. Using confocal microscopy, TPT fluorescence was monitored to determine the accumulation of drug within TES. These studies showed TES, being more reflective of the in vivo tumor microenvironment, were more sensitive to LTPT in comparison to free TPT with radiation. More importantly, the response of TES to low-dose metronomic TPT with radiation was comparable to similar treatment with LTPT. This TES study suggests nanoparticle formulations designed for extended release of drug can simulate LDMC in vivo. More... »

PAGES

15236

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/srep15236

    DOI

    http://dx.doi.org/10.1038/srep15236

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1031988596

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/26468877


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