Development and brain delivery of chitosan-PEG nanoparticles functionalized with the monoclonal antibody OX26

2005-11-01
Aktas, Y
Yemisci, M
Andrieux, K
Gursoy, RN
Alonso, MJ
Fernandez-Megia, E
Novoa-Carballal, R
Quinoa, E
Riguera, R
Sargon, MF
Celik, HH
Demir, Ayhan Sıtkı
Hincal, AA
Dalkara, T
Capan, Y
Couvreur, P
The inhibition of the caspase-3 enzyme is reported to increase neuronal cell survival following cerebral ischemia. The peptide Z-DEVD-FMK is a specific caspase inhibitor, which significantly reduces vulnerability to the neuronal cell death. However, this molecule is unable to cross the blood-brain barrier (BBB) and to diffuse into the brain tissue. Thus, the development of an effective delivery system is needed to provide sufficient drug concentration into the brain to prevent cell death. Using the avidin (SA)-biotin (BIO) technology, we describe here the design of chitosan (CS) nanospheres conjugated with poly(ethylene glycol) (PEG) bearing the OX26 monoclonal antibody whose affinity for the transferrin receptor (TfR) may trigger receptor-mediated transport across the BBB. These functionalized CS-PEG-BIO-SA/OX26 nanoparticles (NPs) were characterized for their particle size, zeta potential, drug loading capacity, and release properties. Fluorescently labeled CS-PEG-BIO-SA/OX26 nanoparticles were administered systemically to mice in order to evaluate their efficacy for brain translocation. The results showed that an important amount of nanoparticles were located in the brain, outside of the intravascular compartment. These findings, which were also confirmed by electron microscopic examination of the brain tissue indicate that this novel targeted nanoparticulate drug delivery system was able to translocate into the brain tissue after iv administration. Consequently, these novel nanoparticles are promising carriers for the transport of the anticaspase peptide Z-DEVD-FMK into the brain.
BIOCONJUGATE CHEMISTRY

Suggestions

In planta determination of GaMyb transcription factor as a target of pathogen induced microRNA, mir159
Akkaya, Mahinur; Dagdas, Gulay Gok; Dagdas, Yasin F. (2011-09-01)
One of the molecular mechanisms underlying the plant–pathogen interactions is the regulation of gene expressions in plant responses by microRNAs which are either stimulated or silenced against pathogen attacks. Among the plant miRNAs, we found that mir159 is one of which that differentially expressed upon Blumeria graminis f. sp. hordei (Bgh) infected resistant and susceptible barley lines. The study aims to confirm its role in regulating one of its putative target genes, GaMyb transcription factor, in vivo...
Analyses of extracellular protein production in Bacillus subtilis - II: Responses of reaction network to oxygen transfer at transcriptional level
KOCABAŞ, PINAR; ÇALIK GARCİA, GÜZİDE; Çalık, Pınar; Ozdamar, Tuncer H. (Elsevier BV, 2017-11-15)
Oxygen transfer influences intracellular fluxes which are orchestrated by genome and its transcription in Bacillus subtilis throughout fermentation in recombinant human growth hormone (rhGH) production. Responses of B. subtilis reaction network to oxygen transfer were analysed at transcriptional level with determined transcriptome and calculated intracellular fluxes by the reconstructed genome scale model iBsu1144(rhGH) based on updated gene-enzyme-reaction data. iBsu1144(rhGH) employing 1067 reactions link...
Regulatory effects of alanine-group amino acids on serine alkaline protease production by recombinant Bacillus licheniformis
Çalık, Pınar; Ozdamar, TH (Wiley, 2003-04-01)
Influences of the concentration and addition time of alanine-group amino acids, i.e. alanine, leucine and valine, on serine alkaline protease (SAP) synthesis were investigated by Bacillus licheniformis (DSM 1969) carrying pHV1431::subC in a defined medium to identify the amino acids creating intracellular reaction-rate limitation in SAP production. While the precursors of alanine-group amino acids, pyruvate and alanine, did not affect SAP production considerably within the range 0-15 mM, the addition of leu...
Influence of oxygen transfer on benzaldehyde lyase production by recombinant Escherichia coli BL21(DE3) pLySs
Angardi, Vahideh; Çalık, Pınar; Department of Chemical Engineering (2007)
In this study, the effects of oxygen transfer conditions on the synthesis of the enzyme benzaldehyde lyase as intracellular in recombinant E. coli BL21 (DE3) pLysS was investigated sistematically and a comprehensive model was developed to determine benzaldehyde lyase activity. For this purpose, the research program was carried out in mainly two parts. In the first part of study, the effects of oxygen transfer together with the mass transfer coefficient (KLa), enhancement factor E (=KLa/KLao), volumetric oxy...
Determination and metabolic engineering of rate limiting reactions in aromatic amino acid pathway in Bacillus subtilis for L-phenylaianine production
Guzide, Calik; Yasemin, Demirci; Pinar, Calik; Ozdamar, Tuncer H. (2007-09-01)
Rate limiting reactions in the aromatic-group amino acid pathway (AAAP) in Bacillus subtilis for l-phenylalanine (Phe) production were determined as reported elsewhere (Özçelik-Şenver et al., 2004). The biochemical reactions in the AAAP start with the reaction using phosphoenolpyruvate (PEP) and erythrose 4-phosphate (E4P) synthesised in the glycolysis pathway and the PPP, respectively, leading to the formation of Phe via chorismate by branching at prephenate. The branch-point metabolites E4P supplied in vi...
Citation Formats
Y. Aktas et al., “Development and brain delivery of chitosan-PEG nanoparticles functionalized with the monoclonal antibody OX26,” BIOCONJUGATE CHEMISTRY, pp. 1503–1511, 2005, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/57045.