Flurorescence Study of the Microenvironment of Pyrene Molecules Loaded into Polycaprolactone-block-poly(ethylene oxide) Polymer Nanoparticles and Implications for Drug Delivery
Date
2023-04-28
Authors
Khokhar, Anupjot Singh
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Polymer nanoparticles (PNPs) come across as the next generation drug delivery vehicles owing to their advantages such as biocompatibility, improved therapeutic efficacy and reduced toxicity. These biodegradable nanocarriers can encapsulate potent drugs and deliver them specifically to tumor cells with minimal effect on peripheral healthy tissues. In this thesis, we provide further understanding about how the microenvironment of the PNP core (polarity) which is a critical parameter for drug delivery properties, is affected by various chemical and structural features of the PNPs, including mean size, internal crystallinity, and drug loading. The role of interactions between encapsulated drugs and polymer nanoparticles is established by using a model hydrophobic probe such as pyrene (Py) which is sensitive to the polarity of the microenvironment and gives both qualitative and quantitative information in form of its fluorescence. We investigate the changing internal microenvironment of encapsulated hydrophobic molecules by applying a combination of chemical- and flow-based experimental variables to obtain a set of pyrene-loaded PNPs (Py-PNPs) with a wide range of properties, which are characterized using additional techniques, including dynamic light scattering (DLS), transmission electron microscopy (TEM), and powder x-ray diffraction (XRD).
We investigated specifically the effects of copolymer composition, initial Py:copolymer loading ratio, rPy, on-chip water content, and microfluidic flow rate, Q on the structural properties of PNPs and pyrene fluorescence intensity ratios. For instance, the effect of initial Py:copolymer loading ratio, rPy, showed some clear impacts of increasing loading ratio on the particle size and size distributions leading to decrease in particle size and increase in polydispersity. Moreover, changes in rPy lead to non-monotonic changes both in encapsulation of pyrene and PNP microenvironment changes tracked by intensity ratios. In addition, these experiments went on to establish the relationship between the structural features of nanoparticles at the colloidal length scale (10 – 100 nm) to the molecular scale (partitioning, viscosity, diffusion) which we believe are critical for drug delivery properties of nanoparticles.
Description
Keywords
polymer nanoparticles, fluorescence, pyrene