Abstract
The development of nanoparticle formulations, particularly lipid-based nanoformulations, holds immense potential in drug delivery applications owing to their biocompatibility and versatility. Recent successes, such as lipid nanoparticles (LNPs) in delivering COVID vaccines, underscore their significance. Phosphatidylcholine (PC) lipids, major constituents of cell membranes, possess self-assembling properties, forming various nanostructures including bilayers and micelles. However, understanding the dynamics of lipid-based nanoformulations is crucial for optimizing drug delivery efficiency. One challenge in computational studies of drug targets has been the determination of membrane protein structures. Achieving high drug loading efficiency while maintaining the stability of the micelles is a significant challenge. The ability of the micelles to effectively encapsulate and retain drugs can vary depending on factors such as drug hydrophobicity, micelle composition, and preparation methods.In this thesis, extensive atomistic molecular dynamics simulations were conducted to investigate various lipid-based drug delivery systems, aiming to elucidate the underlying mechanisms governing their behavior and interactions. The focus was on understanding the internal and interfacial structures and properties of micelles, as well as exploring the influence of different lipid compositions on micellar dynamic systems and drug localization within micelles. Our findings elucidate the unique effects of different micelle components on membrane properties, shedding light on the molecular mechanisms underlying drug delivery processes. Understanding how drugs interact with micelles is crucial for optimizing drug delivery systems.
In the subsequent chapter, the complex interplay between drugs and lipid-based micelles was investigated, revealing distinct preferences of Camptothecin (CAMPT) and Doxorubicin (DOX) within micellar environments. Disparities between PP-micelle and PL-micelle systems underscore the significance of lipid composition in dictating micellar stability and dynamics. Detailed analyses of micelle composition, internal structure, and hydration behaviors provide insights for optimizing drug delivery systems. Further investigations in subsequent chapters focus on drug orientation, localization, and hydration behavior within Solid Lipid Nanoparticles (SLN) and Liquid Lipid Nanoparticles (LLN) systems. Results highlight differences between SLN and LLN in drug encapsulation and distribution, offering implications for nanoparticle design and drug delivery efficacy.
In conclusion, the comprehensive exploration of lipid-based drug delivery systems through atomistic molecular dynamics simulations offers valuable insights into their behavior and interactions. Emphasizing the influence of lipid composition on micellar stability and dynamics, this research provides a foundation for the design of lipid-based drug delivery vehicles. Furthermore, the importance of tailoring drug-micelle interactions to specific drug properties is highlighted, with implications for the advancement of drug delivery systems, particularly in the realm of cancer therapy.
| Date of Award | 1 Oct 2024 |
|---|---|
| Original language | English |
| Awarding Institution |
|
| Supervisor | Chris Lorenz (Supervisor) |