Microfluidic Platform for Controlled Synthesis of Polymeric Nanoparticles
Abstract
A central challenge in the development of drug-encapsulated polymeric nanoparticles is the inability to control the mixing processes required for their synthesis resulting in variable nanoparticle physicochemical properties. Nanoparticles may be developed by mixing and nanoprecipitation of polymers and drugs dissolved in organic solvents with nonsolvents. We used rapid and tunable mixing through hydrodynamic flow focusing in microfluidic channels to control nanoprecipitation of poly(lactic- co-glycolic acid)- b-poly(ethylene glycol) diblock copolymers as a model polymeric biomaterial for drug delivery. We demonstrate that by varying (1) flow rates, (2) polymer composition, and (3) polymer concentration we can optimize the size, improve polydispersity, and control drug loading and release of the resulting nanoparticles. This work suggests that microfluidics may find applications for the development and optimization of polymeric nanoparticles in the newly emerging field of nanomedicine.
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High-precision microfluidic and micropatterning techniques for the production of highly mono-disperse nanoparticles with uniform physicochemical properties and greatly reduced batch-to-batch variability are rapidly gaining attention.
“Compared with bulk-synthesis techniques that largely rely on solution-based chemistry, high-precision microfluidic and micropatterning techniques for the production of highly mono-disperse nanoparticles with uniform physicochemical properties and greatly reduced batch-to-batch variability are rapidly gaining attention90,91.”
From How to design preclinical studies in nanomedicine and cell therapy to maximize the prospects of clinical translation (2018) · cites this paper as [90]
In recent years, progress has been made in producing more controlled formulations with size and composition levels compatible with microfluidic systems.
“In the last years, progress has been made in producing more controlled formulations with size and composition levels compatible with microfluidic systems133”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [133]
Lipid nanoparticle-mRNA formulations manufactured by rapid mixing exhibit a stable nanostructure, in which mRNA molecules can be encapsulated in the interior core through electrostatic interactions with the lipids.
“Lipid nanoparticle–mRNA formulations manufactured by rapid mixing exhibit a stable nanostructure17,130,131, in which mRNA molecules can be encapsulated in the interior core through electrostatic interactions with the lipids17,131.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [130]
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- Authors
- Karnik, R., Gu, F., Basto, P., Cannizzaro, C., Dean, L., Kyei-Manu, W., Langer, R., & Farokhzad, O. C.
- Affiliations
- Harvard–MIT Division of Health Sciences and Technology (US)
- Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, Harvard−MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, MIT−Harvard Center for Cancer Nanotechnology Excellence, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, and Laboratory of Nanomedicine and...
- Corresponding author
- Farokhzad, Omid C.
- Venue
- Nano Letters
- Publisher
- American Chemical Society (ACS)
- Published
- 2008-07-26
- Volume
- 8
- Issue
- 9
- Pages
- 2906-2912
- ISSN
- 1530-6984 (ISSN-L)
- 1530-6992
- OpenAlex
- W2165555463
- Cited by
- 887
- References
- 27
- Citations by year
- 2026: 32 · 2025: 50 · 2024: 57 · 2023: 56 · 2022: 57 · 2021: 72 · 2020: 61 · 2019: 84 · 2018: 54 · 2017: 64 · 2016: 62 · 2015: 43 · 2014: 41 · 2013: 46 · 2012: 47
- FWCI
- 8.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nano Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5u54ca119349-05)
- National Cancer Institute (CA 119349)
- National Institute of Biomedical Imaging and Bioengineering (K08EB003647, EB003647)
- 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
- polymeric nanoparticles, microfluidic mixing, flow focusing, nanoprecipitation, drug delivery, controlled drug release, nanoparticle size control, polydispersity, drug loading, nanomedicine
- MeSH terms
- Particle Size, Polymers, Chemical Precipitation, Microfluidics, Nanoparticles
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