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A high-performance magnetic resonance imaging T2 contrast agent
KTH, School of Information and Communication Technology (ICT), Material Physics, Functional Materials, FNM.
Show others and affiliations
2007 (English)In: Advanced Materials, ISSN 0935-9648, E-ISSN 1521-4095, Vol. 19, no 14, 1874-1878 p.Article in journal (Refereed) Published
Abstract [en]

A high-performance magnetic resonance imaging T-2 contrast agent has been prepared via phase transfer of hydrophobic superparamagnetic iron oxide nanoparticles (SPIONs) to an aqueous solution by using Pluronic F127 copolymers. As seen in the figure, a hierarchical structure of the surface coating is formed and proven to be a crucial characteristic to enhance not only water dispersibility, but also the efficacy as a T-2 contrast agent.

Place, publisher, year, edition, pages
2007. Vol. 19, no 14, 1874-1878 p.
Keyword [en]
superparamagnetic iron-oxide, aqueous-solutions, block-copolymers, nanocrystals, nanoparticles, water, mri, size, micelles, media
National Category
Engineering and Technology
Identifiers
URN: urn:nbn:se:kth:diva-7079DOI: 10.1002/adma.200602326ISI: 000248323800018Scopus ID: 2-s2.0-34547480782OAI: oai:DiVA.org:kth-7079DiVA: diva2:11983
Note
QC 20100721Available from: 2007-05-11 Created: 2007-05-11 Last updated: 2017-12-14Bibliographically 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. Nanoparticles for multifunctional drug delivery systems
Open this publication in new window or tab >>Nanoparticles for multifunctional drug delivery systems
2007 (English)Licentiate thesis, comprehensive summary (Other scientific)
Abstract [en]

Multifunctional drug delivery systems incorporated with stimuli-sensitive drug release, magnetic nanoparticles and magnetic resonance (MR) T2 contrast agents is attracting increasing attention recently. In this thesis, works on polymer nanospheres response to temperature change, superparamagnetic iron oxide nanoparticles (SPION)/polymeric composite materials for MR imaging contrast agents are summarized.

A “shell-in-shell” polymeric structure has been constructed through a “modified double-emulsion method”. Thermosensitive inner shell is comprised of poly(N-isopropylacrylamide) which undergoes phase transition at body temperature. Such a feature could facilitate drug release at an elevated temperature upon administration. Furthermore, the dual-shell structure is covered by a layer of gold nanoparticles. According to the cytotoxicity tests, the biocompatibility is shown to be enhanced due to the layer of gold.

SPION have been prepared using a high temperature decomposition method. Particle growth of SPION is monitored by transmission electron microscope and synchrotron X-ray diffraction. Poly(L,L-lactide)@SPION (PLLA@SPION) composite particles have been prepared through surface-initiated ring-opening polymerization which has been developed in our lab. For biomedical applications, it is essential to transfer the particles to physiological solutions from organic solutions. Phase transfer of SPION has been carried out by utilizing small molecules. Stability at the neutral pH is of large concern for such transfer systems. A novel phase transfer agent, Pluronic F127 (PF127), a triblock copolymer has been applied and the stability of the aqueous PF127@oleic acid (OA)@SPION solution has been greatly enhanced over a broad pH range. Most interestingly, PF127@OA@SPION show remarkable efficacy as T2 contrast agents as indicated by relaxometric measurements compared with commercially available products.

Place, publisher, year, edition, pages
Stockholm: KTH, 2007. x, 66 p.
Keyword
drug delivery, stimuli-sensitive, SPION, PLLA, PNIPAAm, gold, MRI, cytotoxicity, Pluronic, phase transfer
National Category
Materials Chemistry
Identifiers
urn:nbn:se:kth:diva-4369 (URN)978-91-7178-659-3 (ISBN)
Presentation
2007-05-22, Sal B2, KTH, Brinellvägen 23, Stockholm, 10:00 (English)
Opponent
Supervisors
Note
QC 20101115Available from: 2007-05-11 Created: 2007-05-11 Last updated: 2010-11-15Bibliographically approved

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