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Biodistribution of biodegradable polymeric nano-carriers loaded with busulphan and designed for multimodal imaging
KTH, School of Information and Communication Technology (ICT), Materials- and Nano Physics, Functional Materials, FNM. Karolinska Institutet (KI), Sweden.ORCID iD: 0000-0001-8887-9141
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2016 (English)In: Journal of Nanobiotechnology, ISSN 1477-3155, Vol. 14, no 1, article id 82Article in journal (Refereed) Published
Abstract [en]

Background: Multifunctional nanocarriers for controlled drug delivery, imaging of disease development and follow-up of treatment efficacy are promising novel tools for disease diagnosis and treatment. In the current investigation, we present a multifunctional theranostic nanocarrier system for anticancer drug delivery and molecular imaging. Superparamagnetic iron oxide nanoparticles (SPIONs) as an MRI contrast agent and busulphan as a model for lipophilic antineoplastic drugs were encapsulated into poly (ethylene glycol)-co-poly (caprolactone) (PEG-PCL) micelles via the emulsion-evaporation method, and PEG-PCL was labelled with VivoTag 680XL fluorochrome for in vivo fluorescence imaging. Results: Busulphan entrapment efficiency was 83% while the drug release showed a sustained pattern over 10 h. SPION loaded-PEG-PCL micelles showed contrast enhancement in T-2*-weighted MRI with high r(2)* relaxivity. In vitro cellular uptake of PEG-PCL micelles labeled with fluorescein in J774A cells was found to be time-dependent. The maximum uptake was observed after 24 h of incubation. The biodistribution of PEG-PCL micelles functionalized with VivoTag 680XL was investigated in Balb/c mice over 48 h using in vivo fluorescence imaging. The results of real-time live imaging were then confirmed by ex vivo organ imaging and histological examination. Generally, PEG-PCL micelles were highly distributed into the lungs during the first 4 h post intravenous administration, then redistributed and accumulated in liver and spleen until 48 h post administration. No pathological impairment was found in the major organs studied. Conclusions: Thus, with loaded contrast agent and conjugated fluorochrome, PEG-PCL micelles as biodegradable and biocompatible nanocarriers are efficient multimodal imaging agents, offering high drug loading capacity, and sustained drug release. These might offer high treatment efficacy and real-time tracking of the drug delivery system in vivo, which is crucial for designing of an efficient drug delivery system.

Place, publisher, year, edition, pages
BioMed Central, 2016. Vol. 14, no 1, article id 82
Keywords [en]
Biodegradable polymer, Drug delivery, Magnetic resonance imaging, In vivo fluorescence imaging, Biodistribution, Busulphan, Cancer
National Category
Microbiology
Identifiers
URN: urn:nbn:se:kth:diva-200409DOI: 10.1186/s12951-016-0239-0ISI: 000391072700002Scopus ID: 2-s2.0-85006482286OAI: oai:DiVA.org:kth-200409DiVA, id: diva2:1069046
Funder
Swedish Cancer Society, CAN2014/759
Note

QC 20170127

Available from: 2017-01-27 Created: 2017-01-27 Last updated: 2017-01-27Bibliographically approved

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