Author ORCID Identifier
0009-0005-6693-0029
Document Type
Dissertation
Date of Award
5-31-2026
Degree Name
Doctor of Philosophy in Chemical Engineering - (Ph.D.)
Department
Chemical and Materials Engineering
First Advisor
Xiaoyang Xu
Second Advisor
Kamalesh K. Sirkar
Third Advisor
S. Basuray
Fourth Advisor
Xianqin Wang
Fifth Advisor
Yuanwei Zhang
Abstract
Lipid-based nanocarriers have emerged as a cornerstone technology for RNA therapeutics, enabling effective intracellular delivery for applications ranging from vaccination to gene regulation. However, current manufacturing approaches, particularly microfluidic-based platforms, face inherent limitations in scalability, throughput, and structural tunability due to their reliance on confined channel geometries and restricted mixing architectures. Addressing these challenges requires fundamentally new strategies that decouple nanoparticle formation from traditional microscale flow constraints while maintaining precise control over physicochemical properties.
This dissertation presents a comprehensive framework for the design, engineering, and application of advanced lipid-based nanocarriers, centered on a hollow fiber membrane (HFM)—assisted nanopore-mediated assembly platform. By leveraging densely distributed nanoscale pores as parallelized mixing interfaces, this system enables rapid and uniform solvent exchange through radial injection, significantly reducing characteristic mixing length scales and enhancing interfacial area density. This architecture facilitates continuous, high-throughput synthesis of lipid nanoparticles (LNPs) with tunable sizes (-40-200 nm), narrow size distributions (PDI < 0.15), and high encapsulation efficiencies (up to —95%), with particle characteristics directly governed by membrane structural parameters.
Mechanistic investigations combining computational fluid dynamics (CFD) simulations and experimental validation demonstrate that nanoscale injection induces steep concentration gradients and accelerates convective—diffusive coupling, thereby promoting controlled nucleation and lipid self-assembly. Compared to conventional microfluidic systems, the HFM platform exhibits superior scalability through intrinsic parallelization and maintains robust performance during extended continuous operation.
Beyond conventional LNP systems, this dissertation further explores the integration of biomimetic and functional enhancements, including cell membrane-coated nanoparticles for improved biological interfacing and immune modulation, as well as lipid-based nanobubble systems designed for stimulus-responsive delivery and enhanced payload release. These complementary strategies expand the functional landscape of lipid-based nanocarriers, enabling tailored interactions with biological systems and improved therapeutic efficacy.
Collectively, this dissertation establishes a unified engineering paradigm for next-generation nanocarrier manufacturing and design, bridging nanoscale transport phenomena with macroscale process scalability. The proposed approaches provide a versatile and scalable platform for RNA delivery and offer new insights into the rational design of nanomedicine systems for translational and industrial applications.
Recommended Citation
Liu, Zhixiang, "Membrane-engineered nanotherapeutic platforms for drug delivery: Hollow fiber membrane synthesis of lipid nanoparticles, biomimetic nanocarriers, and nanobubbles" (2026). Dissertations. 1884.
https://digitalcommons.njit.edu/dissertations/1884
Included in
Biomedical Engineering and Bioengineering Commons, Chemical Engineering Commons, Materials Science and Engineering Commons
