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Title: The role of physicochemical parameters on polybutylcyanoacrylate nanoparticles' delivery to the central nervous system
Author(s): You, Qing
Referee(s): Sabel, Bernhard A.Look up in the Integrated Authority File of the German National Library
Granting Institution: Otto-von-Guericke-Universität Magdeburg, Fakultät für Naturwissenschaften
Issue Date: 2020
Extent: IV, 79 Seiten
Type: HochschulschriftLook up in the Integrated Authority File of the German National Library
Type: Doctoral Thesis
Exam Date: 2020
Language: English
URN: urn:nbn:de:gbv:ma9:1-1981185920-328911
Subjects: Neurologie
Abstract: Because the blood-brain barrier (BBB) is an obstacle for drug-delivery, carrier systems such as polybutylcyanoacrylate(PBCA) nanoparticles (NPs) have been studied. Yet, little is known of how the physiochemical features such as size and surface charge influence the BBB passage in vivo. Firstly Iused a rat model of in vivoimaging of the retina -which is brain tissue and can reflect the situation at the BBB -to study how size and surface charge determine NPs’ delivery kineticsacross the blood-retina barrier (BRB). Ialso analyzed the co-incubation of NPs with serum in vitroto understand the interactions of NPs with blood. Then Iinvestigated the physicochemical mechanisms underlying these different behaviors of NPs at biological barriers and their influence on the cellular distribution. Retinal whole-mounts from rats injected in vivowith flurescent NPs were processed for retina imaging ex vivoto obtain a detailed distribution of NPs with cellular resolutionin retinal tissue. In addition, Ianalyzed the NPs’body distribution in vivoto explore the systematic interactions.The key results are as follows:Minor changes in composition of poloxamer 188-modified, DEAE-dextran-stabilized (PDD) PBCA NPs, although only slightly altering the physicochemical parameters, such as size or surface charge, substantially influence NPs’ delivery kinetics across the BRB in vivo. Decreasing the Z-average sizefrom 272 nm to 172 nm by centrifugation reduced the BRB passage of the NPs substantially. Varying the zeta-potential within the narrow range of 0-15 mV by adding different amounts of stabilizer revealed that 0 mV and 15 mV were less desirable than 5 mV which facilitated the BRB passage.NPs with medium charge and small sizewere relatively stable in blood, while other NP variations rapidly agglomerated or degraded.In line with the in vivoimaging results, NPs with larger size and medium surface AbstractIIcharge accumulated more readily in brain tissue and they could be more easily detectedin retinalganglion cells (RGCs), demonstrating the suitability of these NPs for drug delivery into neurons. Other NP variations accumulated more in peripheral organs which may reduce the passage of these particles into brain tissue via a “steal effect”-mechanism.Thus, systemic interactions significantly determine the potential of NPs to deliver markers or drugs to the central nervous system (CNS). In this way, minor changes of NPs’ physicochemical parameters can significantly impact alterations in their rate of brain/body biodistribution.
Open Access: Open access publication
License: (CC BY-SA 4.0) Creative Commons Attribution ShareAlike 4.0
Appears in Collections:Fakultät für Naturwissenschaften

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