Optimization of PLGA nanoparticle formulation via microfluidic and batch nanoprecipitation techniques

Type
01A - Journal article
Editors
Editor (Corporation)
Supervisor
Parent work
Micromachines
Special issue
DOI of the original publication
Link
Series
Series number
Volume
16
Issue / Number
9
Pages / Duration
1-22
Patent number
Publisher / Publishing institution
MDPI
Place of publication / Event location
Edition
Version
Programming language
Assignee
Practice partner / Client
Abstract
Polymeric nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) are widely used in drug delivery, yet scalable and reproducible production methods remain a major challenge. In this study, we combine experimental nanoprecipitation and computational fluid dynamics (CFD) modeling to optimize PLGA nanoparticle formulation using both traditional batch and microfluidic methods. While Design of Experiments (DoE) was used to optimize the batch process, microfluidic mixing was systematically explored by varying flow parameters such as the flow rate ratio (FRR) and total flow rate (TFR). We compared two microfluidic mixer designs with Y-junction and three-inlet junction geometries to evaluate their impact on the mixing efficiency and nanoparticle formation. Experimental results revealed that the three-inlet design produced smaller, more uniform nanoparticles with superior post-lyophilization stability. CFD simulations confirmed these findings by displaying velocity fields and PLGA concentration gradients, demonstrating significantly more homogeneous mixing and efficient interfacial contact in the three-inlet configuration. Furthermore, simulated outlet concentrations were used to predict the nanoparticle size via theoretical modeling, which closely agreed with the experimental data. This integrated approach highlights the importance of microfluidic geometry in controlling nanoparticle nucleation dynamics and provides a framework for rational design of scalable nanomedicine production systems.
Keywords
PLGA nanoparticles, Nanoprecipitation, Design of experiments, Microfluidics, Computational fluid dynamics
Project
Event
Exhibition start date
Exhibition end date
Conference start date
Conference end date
Date of the last check
ISBN
ISSN
2072-666X
Language
English
Created during FHNW affiliation
Yes
Strategic action fields FHNW
Publication status
Published
Review
Peer review of the complete publication
Open access category
Gold
License
'https://creativecommons.org/licenses/by/4.0/'
Citation
Kozalak, G., Heyat Davoudian, S., Natsaridis, E., Gogniat, N., Koşar, A., & Tagit, O. (2025). Optimization of PLGA nanoparticle formulation via microfluidic and batch nanoprecipitation techniques. Micromachines, 16(9), 1–22. https://doi.org/10.3390/mi16090972