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Nanoparticles for multifunctional drug delivery systems
KTH, School of Chemical Science and Engineering (CHE), Chemistry.
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 [en]
drug delivery, stimuli-sensitive, SPION, PLLA, PNIPAAm, gold, MRI, cytotoxicity, Pluronic, phase transfer
National Category
Materials Chemistry
Identifiers
URN: urn:nbn:se:kth:diva-4369ISBN: 978-91-7178-659-3 (print)OAI: oai:DiVA.org:kth-4369DiVA: diva2:11985
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
List of papers
1. Thermosensitive nanospheres with a gold layer revealed as low-cytotoxic drug vehicles
Open this publication in new window or tab >>Thermosensitive nanospheres with a gold layer revealed as low-cytotoxic drug vehicles
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2005 (English)In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 21, no 20, 9346-9351 p.Article in journal (Refereed) Published
Abstract [en]

In this paper, the positive effect of a gold layer on cell viability is demonstrated by examining the results given by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfop henyl)-2H-tetrazolium (MTS) assay and two-color cell fluorescence viability (TCCV) assay. These cytotoxicity tests were performed with human cervical adenocarcinoma cells (HeLa cell line) and transformed African green monkey kidney fibroblast cells (Cos-7 cell line). To fabricate the nanostructures as drug vehicles, first, poly((L),(L)-lactidec-co-ethylene glycol) (PLLA-PEG) and poly(N-isopropylacrylamide-co-(D),(D)-lactide) (PNIPAAm-PDLA) were synthesized, and then two kinds of thermosensitive nanospheres comprising "shell-in-shell" structures without a gold layer (PLLA-PEG@PNIPAAm-PDLA) and with a gold layer (Au@PLLA-PEG@PNIPAAmPDLA) were constructed by a modified double-emulsion method (MDEM). Both of them displayed a unique thermosensitive character exhibiting the lower critical solubility temperature (LCST) at 36.7 degrees C which was confirmed by LTV-vis spectroscopy and differential scanning calorimetry (DSC). The release profiles of entrapped bovine serum albumin (BSA) were monitored at 22 and 37 degrees C, respectively, to reveal the thermal dependence on the release rate. In cell viability tests, both PLLA-PEG@PNIPAAm-PDLA and Au@PLLAPEGCd)PNIPAAm-PDLA showed excellent cell viability, and furthermore, Au@PLLA-PEG@PNIPAAmPDLA, particularly at high doses, exhibited more enhanced cell viability than PLLA-PEGCa)PNTPAAm-PDLA. This effect is mainly attributed to the gold layer which binds the protein molecules first and consequently facilitates transmembrane uptake of essential nutrients in the cell media, resulting in favorable cell proliferation.

Keyword
colorimetric detection, bicinchoninic acid, silver-enhancement, polymeric micelles, block-copolymers, nanoparticles, delivery, surface, poly(n-isopropylacrylamide), cells
National Category
Materials Chemistry
Identifiers
urn:nbn:se:kth:diva-12080 (URN)10.1021/la051069t (DOI)000232080100054 ()2-s2.0-26444590043 (Scopus ID)
Note
QC 20100720Available from: 2010-03-03 Created: 2010-03-02 Last updated: 2017-12-12Bibliographically approved
2. A high-performance magnetic resonance imaging T2 contrast agent
Open this publication in new window or tab >>A high-performance magnetic resonance imaging T2 contrast agent
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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.

Keyword
superparamagnetic iron-oxide, aqueous-solutions, block-copolymers, nanocrystals, nanoparticles, water, mri, size, micelles, media
National Category
Engineering and Technology
Identifiers
urn:nbn:se:kth:diva-7079 (URN)10.1002/adma.200602326 (DOI)000248323800018 ()2-s2.0-34547480782 (Scopus ID)
Note
QC 20100721Available from: 2007-05-11 Created: 2007-05-11 Last updated: 2010-11-15Bibliographically approved
3. The importance of an endotoxin-free environment during the production of nanoparticles used in medical applications
Open this publication in new window or tab >>The importance of an endotoxin-free environment during the production of nanoparticles used in medical applications
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2006 (English)In: Nano letters (Print), ISSN 1530-6984, E-ISSN 1530-6992, Vol. 6, no 8, 1682-1686 p.Article in journal (Refereed) Published
Abstract [en]

We investigated the effect of spherical gold nanoparticles on immature dendritic cells (DCs). Conventionally produced nanoparticles had a maturating effect on the DCs-a result of lipopolysaccharide (LPS) contamination. By modification of the production process, low-LPS particles were obtained, which had practically no effect on phenotypic maturation or cytokine production of the DCs. Our findings emphasize the importance of high purity in the production of nanoparticles, since possible contaminants may interfere with the assessment of biological/medical effects. They also highlight that nanoparticles can function as carriers of immune modulating contaminants.

Keyword
human dendritic cells, gold, immunity, lipopolysaccharide, contamination, maturation, particles, receptor, innate, metal
National Category
Materials Chemistry
Identifiers
urn:nbn:se:kth:diva-12100 (URN)10.1021/nl060860z (DOI)000239623900019 ()2-s2.0-33748329694 (Scopus ID)
Note
QC 20100721Available from: 2010-03-03 Created: 2010-03-03 Last updated: 2017-12-12Bibliographically approved

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