Rapid microwave-assisted synthesis of sub-30nm lipid nanoparticles.
OBJECTIVE
Accessing the phase inversion temperature by microwave heating may enable the rapid synthesis of small lipid nanoparticles.


METHODS
Nanoparticle formulations consisted of surfactants Brij 78 and Vitamin E TPGS, and trilaurin, trimyristin, or miglyol 812 as nanoparticle lipid cores. Each formulation was placed in water and heated by microwave irradiation at temperatures ranging from 65°C to 245°C. We observed a phase inversion temperature (PIT) for these formulations based on a dramatic decrease in particle Z-average diameters. Subsequently, nanoparticles were manufactured above and below the PIT and studied for (a) stability toward dilution, (b) stability over time, (c) fabrication as a function of reaction time, and (d) transmittance of lipid nanoparticle dispersions.


RESULTS
Lipid-based nanoparticles with distinct sizes down to 20-30nm and low polydispersity could be attained by a simple, one-pot microwave synthesis. This was carried out by accessing the phase inversion temperature using microwave heating. Nanoparticles could be synthesized in just one minute and select compositions demonstrated high stability. The notable stability of these particles may be explained by the combination of van der Waals interactions and steric repulsion. 20-30nm nanoparticles were found to be optically transparent.
Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, NC, United States; Department of Radiology, University of North Carolina at Chapel Hill, NC, United States. Electronic address: ssdunn@unc.edu.
Stuart S
SS
Dunn
Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, NC, United States; Department of Radiology, University of North Carolina at Chapel Hill, NC, United States. Electronic address: denisrbv@email.unc.edu.
Denis R
DR
Beckford Vera
Center for Nanotechnology in Drug Delivery, Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, United States. Electronic address: benhabs@email.unc.edu.
S Rahima
SR
Benhabbour
Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, NC, United States; Department of Radiology, University of North Carolina at Chapel Hill, NC, United States; The Carolina Institute for Nanomedicine, University of North Carolina at Chapel Hill, NC, United States. Electronic address: parrotmc@email.unc.edu.
Matthew C
MC
Parrott
Lipid nanoparticle; Microwave synthesis; Optical transparency; Sub-30nm