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Cited by 37Nanoparticle-Based Drug DeliveryInnovative Microfluidic and Catalytic Techniques InnovationMicrofluidic and Capillary Electrophoresis Applications

Microfluidic approaches for producing lipid-based nanoparticles for drug delivery applications

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Piunti, Caterina, Cimetta, Elisa·2023·Biophysics Reviews
DOI 10.1063/5.0150345PMC PMC10903496
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Abstract

The importance of drug delivery for disease treatment is supported by a vast literature and increasing ongoing clinical studies. Several categories of nano-based drug delivery systems have been considered in recent years, among which lipid-based nanomedicines, both artificial and cell-derived, remain the most approved. The best artificial systems in terms of biocompatibility and low toxicity are liposomes, as they are composed of phospholipids and cholesterol, the main components of cell membranes. Extracellular vesicles—biological nanoparticles released from cells—while resembling liposomes in size, shape, and structure, have a more complex composition with up to hundreds of different types of lipids, proteins, and carbohydrates in their membranes, as well as an internal cargo. Although nanoparticle technologies have revolutionized drug delivery by enabling passive and active targeting, increased stability, improved solubilization capacity, and reduced dose and adverse effects, the clinical translation remains challenging due to manufacturing limitations such as laborious and time-consuming procedures and high batch-to-batch variability. A sea change occurred when microfluidic strategies were employed, offering advantages in terms of precise particle handling, simplified workflows, higher sensitivity and specificity, and good reproducibility and stability over bulk methods. This review examines scientific advances in the microfluidics-mediated production of lipid-based nanoparticles for therapeutic applications. We will discuss the preparation of liposomes using both hydrodynamic focusing of microfluidic flow and mixing by herringbone and staggered baffle micromixers. Then, an overview on microfluidic approaches for producing extracellular vesicles and extracellular vesicles-mimetics for therapeutic applications will describe microfluidic extrusion, surface engineering, sonication, electroporation, nanoporation, and mixing. Finally, we will outline the challenges, opportunities, and future directions of microfluidic investigation of lipid-based nanoparticles in the clinic.

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  • Hydrophobic, small-molecule drugs can be directly loaded into EVs by passive mixing.

    “Like the co-incubation of cargoes with parent cells, hydrophobic, small-molecule drugs can be directly loaded into EVs by passive mixing [221].”

    From Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions (2024) · cites this paper as [221]

    The Introduction states that EVs can encapsulate hydrophobic contents, supporting the cargo-related part of the claim. It does not say that hydrophobic small-molecule drugs can be loaded directly by passive mixing; the paper’s described direct-loading method uses mechanical permeabilization instead (Microfluidic Nanoporation; page not provided). (LLM, conf=0.85)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Piunti, C., & Cimetta, E.
Affiliations
University of Padua (IT)
Corresponding author
Cimetta, Elisa
ORCID
Venue
Biophysics Reviews
Publisher
AIP Publishing
Published
2023-09-01
Volume
4
Issue
3
Pages
031304-031304
ISSN
2688-4089 (ISSN-L)
DOI
10.1063/5.0150345
PMC
PMC10903496
OpenAlex
W4386830239
Cited by
37
References
3
Citations by year
2026: 17 · 2025: 18 · 2024: 2
FWCI
0.65
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Biophysics Reviews (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Padua Research Archive (University of Padova) (submittedVersion, cc-by)
Funders
European Research Council (759467)
Topics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Physical Sciences › Engineering › Biomedical Engineering › Innovative Microfluidic and Catalytic Techniques Innovation
  • Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Capillary Electrophoresis Applications
Keywords
microfluidics, lipid nanoparticles, liposomes, extracellular vesicles, drug delivery, hydrodynamic focusing, micromixer, surface engineering, electroporation, sonication, clinical translation

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