Novel devices for evaluating nanomedicine biological fate

Student thesis: Doctoral Thesis

Abstract

The formation of the protein (biomolecular) corona around nanoparticles is a phenomenon of high current interest in pharmaceutical sciences, as the composition of the protein corona is known to influence nanoparticle biological fate. The protein corona can be modified by many physicochemical parameters, including the presence of fluid shear, leading to differences in both thickness and composition when results from static in vitro and dynamic in vivo studies are compared. This thesis considers the protein corona that develops around the biologically compatible poly (lactic-co-glycolic) acid (PLGA) nanoparticles following coincubation with biological media (foetal bovine serum, human serum) before moving on to study the physiological forces experienced by these nanoparticles in vivo immediately following the introduction into the body via several clinically used vascular access devices. This work presents (for the first time) the use of resonant mass measurement to analyse protein corona formation around submicron polymeric nanoparticles and shows its use as an orthogonal method alongside particle tracking analysis. Computational fluid dynamics (CFD) has been used to study blood flow in vivo. Finally, the insights obtained here were then used as input parameters to guide the design and development of a 3D-printed microfluidic device capable of subjecting nanoparticles to physiologically relevant fluid shear. This device will give rise to a protein corona with a structure and composition more like that obtained in vivo without requiring animal-based pre-clinical studies. In this work, it has been shown that there are statistically significant temporal, temperature and protein concentration effects on the composition of the protein corona around PLGA nanoparticles (0 vs 24hrs, p=
Date of Award24 Jul 2024
Original languageEnglish
Awarding Institution
  • University Of Strathclyde
SponsorsUniversity of Strathclyde
SupervisorCameron Brown (Supervisor) & Blair Johnston (Supervisor)

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