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Biodistribution of Busulphan Loaded Biodegradable Nano-carrier Designed for Multimodal Imaging
KTH, School of Information and Communication Technology (ICT), Materials- and Nano Physics, Functional Materials, FNM.ORCID iD: 0000-0001-8887-9141
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Multifunctional nanocarriers for pathological site imaging and regulated drug delivery are increasingly promising for disease diagnosis and treatment. We developed 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 an antineoplastic agent were encapsulated into poly (ethylene glycol)-co-poly (caprolactone) (PEG-PCL) nanoparticles (NPs) via the emulsion-evaporation method. Busulphan entrapment efficiency was 83% and the drug release showed a sustained pattern over 10 hours. SPION loaded-PEG-PCL NPs showed contrast enhancement in T2*-weighted MRI with high r2* relaxivity. In vitro time-dependent cellular PEG-PCL NP uptake was observed in macrophage cells (J774A). PEG-PCL NPs were further functionalized with VivoTag 680XL Fluorochrome for in vivo fluorescence imaging for study of their biodistribution in Balb/c mice over 48 h. The results of real-time imaging were then confirmed by ex vivo organ imaging and histological examination. Generally, PEG-PCL NPs were highly distributed in the lungs until 4 h post intravenous administration, then redistributed and accumulated in liver and spleen until 48 h. No pathological impairment was found in the studied tissues. Thus, PEG-PCL NPs as biodegradable and biocompatible nanocarriers are an efficient multimodal imaging agent, offer high drug loading capacity, and provide the possibility of disease treatment.

Keyword [en]
Biodegradable polymer, drug delivery, magnetic resonance imaging, cellular uptake, cytotoxicity, biodistribution, in vivo fluorescence imaging, fluorescence/CT imaging co- registration
National Category
Physical Sciences
Research subject
URN: urn:nbn:se:kth:diva-187049OAI: diva2:928798

QC 20160518

Available from: 2016-05-16 Created: 2016-05-16 Last updated: 2016-05-18Bibliographically approved
In thesis
1. Synthesis of Polymeric Nanocomposites for Drug Delivery and Bioimaging
Open this publication in new window or tab >>Synthesis of Polymeric Nanocomposites for Drug Delivery and Bioimaging
2016 (English)Licentiate thesis, comprehensive summary (Other academic)
Abstract [en]

Nanomaterials have gained great attention for biomedical applications due to their extraordinary physico-chemical and biological properties. The current dissertation presents the design and development of multifunctional nanoparticles for molecular imaging and controlled drug delivery applications which include biodegradable polymeric nanoparticles, superparamagnetic iron oxide nanoparticles (SPION)/polymeric nanocomposite for magnetic resonance imaging (MRI) and drug delivery, manganese-doped zinc sulfide (Mn:ZnS) quantum dots (QDs)/ SPION/ polymeric nanocomposites for fluorescence imaging, MRI and drug delivery.Bioimaging is an important function of multifunctional nanoparticles in this thesis. Imaging probes were made of SPION and Mn:ZnS QDs for in vitro and in vivo imaging. The SPION have been prepared through a high temperature decomposition method to be used as MRI contrast agent. SPION and Mn:ZnS were encapsulated into poly (lactic-co-glycolic) acid (PLGA) nanoparticles during the particles formation. The hydrophobic model drug, busulphan, was loaded in the PLGA vesicles in the composite particles. T2*-weighted MRI of SPION-Mn:ZnS-PLGA phantoms exhibited enhanced negative contrast with r2* relaxivity of 523 mM-1 s-1. SPION-Mn:ZnS-PLGA-NPs have been successfully applied to enhance the contrast of liver in rat model.The biodegradable and biocompatible poly (ethylene glycol)-co-poly (caprolactone) (PEG-PCL) was used as matrix materials for polymeric nanoparticles -based drug delivery system. The PEG-PCL nanoparticles have been constructed to encapsulate SPION and therapeutic agent. The encapsulation efficiency of busulphan was found to be ~ 83 %. PEG-PCL nanoparticles showed a sustained release of the loaded busulphan over a period of 10 h. The SPION-PEG-PCL phantoms showed contrast enhancement in T2*-weighted MRI. Fluorescein-labeled PEG-PCL nanoparticles have been observed in the cytoplasm of the murine macrophage cells (J774A) by fluorescence microscopy. Around 100 % cell viability were noticed for PEG-PCL nanoparticles when incubated with HL60 cell line. The in vivo biodistribution of fluorescent tagged PEG-PCL nanoparticles demonstrated accumulation of PEG-PCL nanoparticles in different tissues including lungs, spleen, liver and kidneys after intravenous administration.

Place, publisher, year, edition, pages
KTH Royal Institute of Technology, 2016. 42 p.
Biodegradable polymers, SPION, QDs, drug delivery, cytotoxicity, MRI, in vivo fluorescence imaging, biodistribution
National Category
Electrical Engineering, Electronic Engineering, Information Engineering
Research subject
urn:nbn:se:kth:diva-186300 (URN)978-91-7595-930-6 (ISBN)
2016-06-10, Sal C, Isafjordsgatan 26, Kista, Stockholm, 10:00 (English)

QC 20160516

Available from: 2016-05-16 Created: 2016-05-09 Last updated: 2016-05-17Bibliographically approved

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Asem, Heba
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