Di Spirito, Nicola Antonio (2024) Handling the self-assembly of Pluronic F68 for diverse applications. [Tesi di dottorato]

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Abstract

Pluronics, alias poloxamers, are synthetic amphiphilic copolymers owning a triblock structure with a central hydrophobic poly(propylene oxide) (PPO) segment linked to two lateral hydrophilic poly(ethylene oxide) (PEO) chains. Commercially, Pluronics exist in numerous types according to the length of PPO and PEO chains, exhibiting different behaviour and phase diagrams in solution. Concentrated aqueous solutions of Pluronics form thermoreversible gel-like systems. Properties such as versatility, biocompatibility, nontoxicity, thermosensitivity and self-assembling behaviour make them extremely attractive for numerous applications. The main actor of this experimental work is Pluronic F68 (aka Poloxamer 188), and its self-assembly in solution is herein exploited for diverse applications. In particular, aqueous solutions of Pluronic F68 undergo a reversible thermal phase transition, moving from a micellar liquid phase to a crystalline body-centered cubic (BCC) solid structure with increasing temperature. First, this thesis illustrates Pluronics and their phase behaviour, accounting for the influence of external additives. Different strategies to endow Pluronics with improved and extra properties are described. A synopsis of useful experimental methodologies for understanding the flow properties of Pluronic-based systems is presented, providing a practical guide to their experimental characterization. Significant advances of Pluronic-based materials are reviewed to elucidate their role in diverse applications, ranging from drug delivery and tissue engineering to bioprinting, cell cultures, and personal care industry. Then, the experimental results of this work are presented. First, pronounced attention is paid to the investigation of aqueous solutions of Pluronic F68 in the presence of different drugs, i.e., diclofenac sodium, ibuprofen, ibuprofen sodium, and diclofenac potassium, in order to optimize the synthesis of novel biocompatible drug nanocarriers, and test the effects of the drugs on the system rheological, morphological, and structural properties. The combination of complementary experimental methodologies, namely, rheology and small-angle X-ray scattering (SAXS) allows to identify novel potential drug delivery systems, able to store huge amounts of drug molecules. Furthermore, Pluronic F68 is tested as release vehicle for percutaneous administration of diclofenac sodium. The experimental examination via static Franz-type diffusion cell of the drug release process – coupled with the modeling through a mass balance in pseudostationary conditions – allows for the measurement of the diclofenac sodium diffusion coefficient. This strategy adopts the Franz cell for measuring molecular diffusion, thus avoiding more complicated and expensive techniques. Moreover, the phase transitions of Pluronic F68 solutions in water (H2O) and heavy water (D2O) are observed via experimental rheology and SAXS, to discover the isotope effect on the system phase and conformational properties. The experimental description evidences that the phase properties of such materials can be strongly altered by the isotopic composition of the solvent, which also has a strong significance in common experimental techniques often implicitly assuming no thermodynamical and physical chemistry modifications by isotopic substitution. Then, innovative self-assembling electrically conductive hydrogels (ECHs) holding antimicrobial properties for biomedical applications based on Pluronic F68 are synthesized. Pluronic F68 is mixed with increasing concentrations of conductive poly(3,4-ethylenedioxythiophene):poly-(styrenesulfonate) (PEDOT:PSS) and silver, and the rheology and morphology of the resulting Pluronic F68-based systems as function of temperature and concentration is assessed. The presence of PEDOT:PSS allows for the conversion of a poorly conductive hydrogel into an electrically conductive one. Furthermore, silver donates to the hydrogels antimicrobial properties, as proven by positive growth inhibitory tests against multi-drug resistant Staphylococcus aureus, a major human pathogen. Finally, a highly catalytic three-dimensional (3D) nanostructured platinum electrode for catalysis, sensing and energy harvesting is synthesized by using the Pluronic F68 3D BCC phase as a soft-template. The properties and morphology of the Pt nanostructured electrode are analyzed by electrochemical investigation, SAXS, Transmission Electron Microscopy (TEM), and Scanning Electron Microscope (SEM), and its electrochemical performance towards oxygen reduction reaction (ORR) is assessed. The water-based template provides a chemical-free, eco-friendly and facile route for ordered mesoporous conductive nanomaterials manufacturing. The results suggest a nanostructure based on the topology of the I-Wrapped Package (I-WP) minimal surface, representing the first case at this length scale from a metallic material. This study is based on the development and experimental investigation of diverse formulations based on Pluronic block copolymers, not intended as just inert materials, but also as systems with functional properties able to revolutionise the paradigm of many technological fields. The use of Pluronic F68 demonstrated in this study is conditio sine qua non for the production of innovative systems potentially able to underpin ongoing research in diverse relevant scientific areas.

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