Investigation of protein corona formation on biodegradable nanocarriers
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Date
2023
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Thesis (M.S.)-Bogazici University. Institute of Biomedical Engineering, 2023.
Abstract
Biodegradable nanocarrier systems are significant tools for drug delivery sys tems since they enable prolonging the therapeutic effect of the chemotherapeutic drug by extending the release over a longer period of time. However, the most significant challenge of these systems is the protein corona (PC), the layer formed around the surface of nanocarriers by the adhesion of plasma proteins when nanocarriers are in jected into the body intravenously. Since the PC structure identifies the nanocarriers’ destiny in the body, it is required to be analyzed the proteins that form the PC struc ture comprehensively. In this study, proteins found in the hard protein corona (HPC) structure of two different biodegradable nanospheres (NSs), poly(lactide-co-glycolide) (PLGA) and polycaprolactone (PCL) NSs, were identified. For this purpose, distinct PLGA and PCL nanoparticles (NPs) were fabricated by miniemulsion/solvent evapo ration method, followed by the characterization by electron microscopy, dynamic light scattering (DLS) and electrophoretic light scattering (ELS). Subsequently, PLGA and PCL NSs were treated with human plasma or FBS to form PC structure. Proteins in PC structures were analyzed by sodium dodecyl sulfate polyacrylamide gel elec trophoresis. Furthermore, each protein in the HPC structure were identified by liquid chromatography-mass spectrometry (LC- MS) and grouped according to their func tions. Moreover, doxorubicin hydrochloride, a significant chemotherapeutic drug, was encapsulated into PLGA NSs. Drug encapsulated NSs were characterized by DLS and ELS. Afterward, the PC structure around the surface of drug encapsulated NSs was formed by treating with human plasma or FBS. The impact of the PC on the drug release behavior of PLGA NSs was investigated at pH 7.4, a critical pH value to mimic the physiological environment. NOTE Keywords : Biodegradable Nanocarriers, Polymer Nanoparticles, Protein Corona.