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MRI of the Cochlea with Superparamagnetic Iron Oxide Nanoparticles Compared to Gadolinium Chelate Contrast Agents in a Rat Mode
KTH, School of Information and Communication Technology (ICT), Microelectronics and Applied Physics, MAP. (Functional Materials)
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2009 (English)In: European Journal of Nanomedicine, ISSN 1662-5986, Vol. 2, no 2, 29-36 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2009. Vol. 2, no 2, 29-36 p.
Keyword [en]
animal, contrast agent, linner ear, fluids, MRI, nanotechnology, neuron
National Category
Engineering and Technology
Identifiers
URN: urn:nbn:se:kth:diva-12106Scopus ID: 2-s2.0-79551699165OAI: oai:DiVA.org:kth-12106DiVA: diva2:302007
Note

QC 20101210

Available from: 2010-03-04 Created: 2010-03-04 Last updated: 2017-04-28Bibliographically approved
In thesis
1. Environment-Sensitive Multifunctional Drug Delivery Systems
Open this publication in new window or tab >>Environment-Sensitive Multifunctional Drug Delivery Systems
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Drug delivery systems (DDS) with multiple functionalities such as environment-sensitive drug release mechanisms and visualization agents have motivated the biomedical community as well as materials chemists for more than a decade. This dissertation is concerned with the development of nanoparticles for multifunctional DDS  to tackle several crucial challenges in these complex systems, including polymeric nanospheres which respond to temperature change, superparamagnetic iron oxide nanoparticles/polymeric composite for magnetic resonance imaging contrast agents and drug carriers, immunoresponse of nanomaterials and injectable magnetic field sensitive ferrogels.

The biocompatible and biodegradable polylactide (PLA) was employed as matrix materials for polymeric nanosphere-based DDS. The thermosensitive polymeric nanospheres have been constructed through a “modified double-emulsion method”. The inner shell containing the thermosensitive poly(N-isopropylacrylamide) (PNIPAAm) undergoes a “hydrophilic-to-hydrophobic” phase transition around the human body temperature. The sensitivity of the polymer to the temperature can facilitate drug release at an elevated temperature upon administration. In addition, gold nanoparticles were assembled on the dual-shell structure to form a layer of gold shell. The cell viability was found to be enhanced due to the gold layer. The immunoresponse of the gold nanoparticles has been considered even if no acute cytotoxicity was observed.

Imaging is another functionality of multifunctional DDS. This work focuses on magnetic resonance imaging (MRI) and involves synthesis and surface modification of superparamagnetic iron oxide nanoparticles (SPIONs) for contrast agents. The SPIONs have been prepared through a high temperature decomposition method. Surface modification was carried out in different ways. Poly(L,L-lactide) (PLLA) was grafted on SPIONs through surface-initiated ring-opening polymerization. The hydrophobic model drug indomethacin was loaded in the PLLA layer of the composite particles. For biomedical applications, it is essential to modify the hydrophobic particles so that they can be dispersed in physiological solutions. A series of protocols including using small charged molecules and amphiphilic polymers has been established. Pluronic F127 (PF127), a triblock copolymer was applied as a phase transfer reagent. Most interestingly, PF127@SPIONs show remarkable efficacy as T2 contrast agents. The PF127@SPIONs have been successfully applied to image the cochlea in a rat model. As another phase transfer reagent, poly(maleic anhydride-alt-octadecene)-graft-PNIPAAm (PMAO-graft-PNIPAAm) was created for surface modification of SPIONs. This new copolymer provides the modified SPIONs with thermosensitivity together with water-dispersibility.

As another form of DDS, ferrogel made of PF127 copolymer and SPIONs was developed. Gelation process depends on the temperature of the SPIONs/PF127 mixture. This property makes it possible to use the ferrogel as an injectable drug carrier. Unlike other ferrogels based on crosslinked polymeric network, the PF127 ferrogel can entrap and release hydrophobic drugs. Application of an external magnetic field is found to enhance the drug release rate. This property can find application in externally stimulated local drug release applications.

Place, publisher, year, edition, pages
Stockholm: KTH, 2010. 86 p.
Series
Trita-ICT/MAP AVH, ISSN 1653-7610 ; 1
National Category
Materials Chemistry
Identifiers
urn:nbn:se:kth:diva-12053 (URN)978-91-7415-576-1 (ISBN)
Public defence
2010-03-19, C2, Electrum, Isafjordsgatan 26, Kista, 10:00 (English)
Opponent
Supervisors
Note
QC20100722Available from: 2010-03-02 Created: 2010-02-26 Last updated: 2010-07-22Bibliographically approved
2. Multifunctional nanomaterials for diagnostic and therapeutic applications
Open this publication in new window or tab >>Multifunctional nanomaterials for diagnostic and therapeutic applications
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In the past few years, the use of nanostructured materials in medical applications hasdramatically increased, both in the research phase and for clinical purposes, due to thepeculiar properties and the ability of such materials to interact at a similar scale withbiological entities. In this thesis, we developed tailored magnetic multifunctionalnanoparticles for diagnostic and therapeutic applications, such as detection ofbiomolecules, simultaneous enhanced magnetic resonance imaging (MRI), fluorescentvisualization and controlled drug release.For sensitive and selective detection of specific biomolecules, thermally blocked ironoxide nanoparticles with tailored magnetic properties were developed. The formation ofsuch nanoparticles has been studied both in terms of size and magnetic behavior in liquidsuspension or in polymer matrixes. These particles with narrow size distribution (averagediameter of 19 nm) were surface functionalized by antigen molecules and were used forthe detection of Brucella antibodies in biological samples. The binding of biomoleculesresults in an increase in the particle’s hydrodynamic diameter, affecting the relaxationbehavior that was monitored by magnetic measurements. This sensing system is a fastand sensitive biosensor with very low detection limits (0.05 μg/mL).Superparamagnetic iron oxide nanoparticles (SPION) have been synthesized withaverage diameter of 10-12 nm, narrow size distribution, high crystallinity and superiormagnetic properties as liquid suspensions or embedded in a bulk transparent magneticnanocomposite. These nanoparticles were synthesized in organic solvents and, after phasetransfer with Pluronic F127 amphiphilic copolymer, show excellent relaxivity properties(high r2/r1 ratio) and great contrast enhancement in T2 weighted MRI, confirmed by invivostudies of rat inner ear.SPION have been used as a component for different multifunctional nanostructures. Thefirst system based on poly (L,L lactide)-methoxy polyethylene glycol (PLLA-mPEG)copolymer has been prepared by an emulsion/evaporation process that lead to polymericnanoparticles containing several imaging agents, such as SPION, quantum dots (QDs)and gold nanorods as well as indomethacin (IMC) as therapeutic payload. With a similarprocedure, but using poly (lactide-co-glycolide) (PLGA-PEG-NH2) copolymer, a secondtype of multifunctional nanoparticles has been obtained. Their size can be tailored from70 to 150 nm varying synthesis parameters, such as the surfactant concentration or waterto oil ratio. Both these polymer-based multifunctional nanoparticles can be visualized byfluorescence microscopy (QDs photoemission) and MRI (SPION magnetization) and theycan be used for photothermal therapy (gold nanorods) and drug delivery. The last systemconsists of SPION nanoparticles coated with PLLA directly on the surface by an in-situpolymerization process. A hydrophobic drug was loaded before the phase transfer withPluronic F127 and these nanoparticles show simultaneous MRI T2 contrast enhancementas well as high drug loading and sustained delivery.Controlling the drug release rate is also a critical parameter for tailored therapeutictreatments, and for this reason we developed a novel drug delivery system based on theintegration of SPION and Pluronic F127 gels. IMC was loaded in the ferrogel (with atailored gelation temperature) and its release rate was triggered by applying an externalmagnetic field owing to the SPION magnetic properties.

Place, publisher, year, edition, pages
Stockholm: KTH, 2010. xii, 70 p.
Series
Trita-ICT/MAP AVH, ISSN 1653-7610 ; 2010:11
National Category
Dentistry
Identifiers
urn:nbn:se:kth:diva-26788 (URN)978-91-7415-803-8 (ISBN)
Public defence
2010-12-17, C2, KTH-Electrum, Isafjordsgatan 24, Kista, 13:30 (English)
Opponent
Supervisors
Note
QC 20101207Available from: 2010-12-07 Created: 2010-11-26 Last updated: 2010-12-07Bibliographically approved

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