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Development of EGF-conjugated liposomes for targeted delivery of boronated DNA-binding agents
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Fysikalisk-kemiska institutionen.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Fysikalisk-kemiska institutionen.
Vise andre og tillknytning
2002 (engelsk)Inngår i: Bioconjugate chemistry, ISSN 1043-1802, E-ISSN 1520-4812, Vol. 13, nr 4, s. 737-743Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Liposomes are of interest as drug delivery tools for therapy of cancer and infectious diseases. We investigated conjugation of epidermal growth factor, EGF, to liposomes using the micelle-transfer method. EGF was conjugated to the distal end of PEG−DSPE lipid molecules in a micellar solution and the EGF−PEG−DSPE lipids were then transferred to preformed liposomes, either empty or containing the DNA-binding compound, water soluble acridine, WSA. We found that the optimal transfer conditions were a 1-h incubation at 60 °C. The final conjugate, 125I-EGF−liposome−WSA, contained approximately 5 mol % PEG, 10−15 EGF molecules at the liposome surface, and 104 to 105 encapsulated WSA molecules could be loaded. The conjugate was shown to have EGF-receptor-specific cellular binding in cultured human glioma cells.

sted, utgiver, år, opplag, sider
2002. Vol. 13, nr 4, s. 737-743
HSV kategori
Identifikatorer
URN: urn:nbn:se:uu:diva-90321DOI: 10.1021/bc0100713OAI: oai:DiVA.org:uu-90321DiVA, id: diva2:162631
Tilgjengelig fra: 2003-04-30 Laget: 2003-04-30 Sist oppdatert: 2018-12-04
Inngår i avhandling
1. Liposomes for Drug Delivery: from Physico-chemical Studies to Applications
Åpne denne publikasjonen i ny fane eller vindu >>Liposomes for Drug Delivery: from Physico-chemical Studies to Applications
2003 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

Physico-chemical characterisation of structure and stability of liposomes intended for drug delivery is the central issue in this thesis. In addition, targeted liposomes to be used in boron neutron capture therapy (BNCT) were developed.

Lysolipids and fatty acids are products formed upon hydrolysis of PC-lipids. The aggregate structure formed upon mixing lysolipids, fatty acids and EPC were characterised by means of cryo-TEM. A relatively monodisperse population of unilamellar liposomes was detected in mixtures containing equimolar concentration of the three components.

The interactions between alternative steric stabilisers (PEO-PPO-PEO copolymers) and conventional PC-and pH-sensitive PE-liposomes were investigated. Whereas the PE-liposomes could be stabilised by the PEO-PPO-PEO copolymers, the PC-liposomes showed an enhanced permeability concomitant with the PEO-PPO-PEO adsorption.

Permeability effects induced by different PEG-stabilisers on EPC liposomes were shown to be dependent on the length of the PEG chain but also on the linkage used to connect the PEG polymer with the hydrophobic membrane anchor.

An efficient drug delivery requires, in most cases, an accumulation of the drug in the cell cytoplasm. The mechanism behind cytosolic drug delivery from pH-sensitive liposomes was investigated. The results suggest that a destabilisation of the endosome membrane, due to an incorporation of non-lamellar forming lipids, may allow the drug to be released.

Furthermore, sterically stabilised liposomes intended for targeted BNCT have been characterised and optimised concerning loading and retention of boronated drugs.

sted, utgiver, år, opplag, sider
Uppsala: Acta Universitatis Upsaliensis, 2003. s. 71
Serie
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1104-232X ; 826
Emneord
Physical chemistry, liposome, steric stabilisation, BNCT, cryo-TEM, EGF, targeting, stability, permeability, pH-sensitive liposomes, triggered release, Fysikalisk kemi
HSV kategori
Forskningsprogram
fysikalisk kemi
Identifikatorer
urn:nbn:se:uu:diva-3390 (URN)91-554-5592-1 (ISBN)
Disputas
2003-05-23, B41, BMC, Uppsala, 10:15
Opponent
Veileder
Tilgjengelig fra: 2003-04-30 Laget: 2003-04-30bibliografisk kontrollert

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