Polymeric nanoparticles as drug delivery systems for blood-brain barrier permeation

Epitropaki, Eirini (2024). Polymeric nanoparticles as drug delivery systems for blood-brain barrier permeation. University of Birmingham. Ph.D.

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Abstract

Neurodegenerative diseases pose a significant and escalating threat, characterized by the progressive degeneration of neurons and cognitive decline. Addressing this challenge requires the development of innovative therapeutic modalities aimed at neural regeneration, contingent upon overcoming the formidable obstacle presented by the blood-brain barrier (BBB). This research explores the utilization of polymeric nanoparticles as tailored drug delivery systems, specifically designed for non-invasive permeation of the BBB.
Methodologically, diblock copolymers serve as foundational components for the self-assembly of polymeric nanoparticles, utilizing a variety of techniques, including flash nanoprecipitation, slow addition, dialysis, and microfluidic systems. However, it was observed that the nanoparticles exhibit increased size and high polydispersity, attributed to kinetic entrapment and the protein corona phenomenon, indicating significant NP-protein interactions. Furthermore, in vivo zebrafish studies revealed acceptable viability and size for PDMA87-b-PLLA30 nanoparticles, though further investigation is warranted.
Crystallization-driven self-assembly (CDSA) was employed to generate diverse morphologies from the aforementioned diblock copolymers, aiming to enhance retention time. Despite the successful acquisition of diamond-shaped and cylindrical microstructures, the restrictive size and challenges associated with the protein corona phenomenon underscore the need for extensive optimization to facilitate BBB permeation.
Additionally, polymerization-induced self-assembly (PISA) nanoparticles underwent comprehensive evaluation, including cytotoxicity, internalization, and permeability studies using an in vitro BBB model. Notably, PISA NP 62 Tf exhibited high levels of endocytosis in the CD34+ cell line, while PISA NP PDMA demonstrated the highest permeability percentage without compromising the integrity of the in vitro BBB model.
Overall, the results demonstrate the versatility of polymeric nanoparticles in enabling BBB penetration, offering promising avenues for targeted drug delivery to the central nervous system (CNS). Through meticulous optimization of nanoparticle design and fabrication methods, this research contributes to the advancement of nanomedicine, with implications for the development of effective therapies for neurodegenerative diseases and beyond.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):