Development of nanoporous packaging for improving stability and pulmonary delivery of vaccine formulations
File(s)
Author(s)
Xiang, Shuning
Type
Thesis
Abstract
Nucleic acid vaccines carried by lipid nanoparticles (LNPs) are a desirable pathway to address worldwide outbreaks, but the required cold-chain storage causes high cost. Functionalised lipid nanoparticles (fLNPs) paired with silica-based nanoporous packaging were explored to improve their thermostability at ambient temperature.
Silica substrates were used to load LNPs coated with amphiphilic, anionic polymers PP75 that enable pH-triggered endosomal escape. Quartz Crystal Microbalance with Dissipation (QCM-D) revealed that a higher temperature was favourable for the PP75 adsorption. There was a micelle-to-unimer change with increasing temperature, and the polymer behaviour also depended on the charge and hydrophobicity of the surface. Similarly, the LNPs with the PP75 coating had the same response to the temperature change as compared to free PP75.
Nanoporous silica with alumina or gold coatings to adjust surface properties was engineered by controlling pore diameter, depth, and distribution to capture nanocarriers during the loading process. On alumina surfaces, by altering the pH from 5.5 to 7.0, over 30% of the fLNPs were unloaded measured by QCM-D, displaying controllable storage at the nanoscale.
Based on fLNP delivery insights, lung-endogenous sugars were evaluated as alternative carriers for pulmonary administration. The aerosol performance of dry powders was optimised by ball milling and blending lactose of various sizes, achieving 70% in fine particle fraction (FPF). The effects of particle size, contact surface and relative humidity (RH) on the triboelectrification behaviour were studied. Pure crystalline lactose acquired a negative charge on stainless steel (SS), polyethylene (PE) and polypropylene (PP), while the selected dry powder of multiple components obtained a positive charge.
Overall, silica-based nanopackaging offers a viable solution for the instability of fLNPs at room temperature and their agglomeration. QCM-D effectively guides substrate selection and monitors interfacial interactions in a changeable environment. Furthermore, pulmonary administration would be a promising route to carry LNP vaccines.
Silica substrates were used to load LNPs coated with amphiphilic, anionic polymers PP75 that enable pH-triggered endosomal escape. Quartz Crystal Microbalance with Dissipation (QCM-D) revealed that a higher temperature was favourable for the PP75 adsorption. There was a micelle-to-unimer change with increasing temperature, and the polymer behaviour also depended on the charge and hydrophobicity of the surface. Similarly, the LNPs with the PP75 coating had the same response to the temperature change as compared to free PP75.
Nanoporous silica with alumina or gold coatings to adjust surface properties was engineered by controlling pore diameter, depth, and distribution to capture nanocarriers during the loading process. On alumina surfaces, by altering the pH from 5.5 to 7.0, over 30% of the fLNPs were unloaded measured by QCM-D, displaying controllable storage at the nanoscale.
Based on fLNP delivery insights, lung-endogenous sugars were evaluated as alternative carriers for pulmonary administration. The aerosol performance of dry powders was optimised by ball milling and blending lactose of various sizes, achieving 70% in fine particle fraction (FPF). The effects of particle size, contact surface and relative humidity (RH) on the triboelectrification behaviour were studied. Pure crystalline lactose acquired a negative charge on stainless steel (SS), polyethylene (PE) and polypropylene (PP), while the selected dry powder of multiple components obtained a positive charge.
Overall, silica-based nanopackaging offers a viable solution for the instability of fLNPs at room temperature and their agglomeration. QCM-D effectively guides substrate selection and monitors interfacial interactions in a changeable environment. Furthermore, pulmonary administration would be a promising route to carry LNP vaccines.
Version
Open Access
Date Issued
2025-08-13
Date Awarded
01/02/2026
License URL
Advisor
Heng, Jerry
Chen, Rongjun
Sponsor
Imperial College London
Publisher Department
Department of Chemical Engineering
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)