The application of lipid nanoparticles in drug delivery and vaccine formulation has opened new frontiers in medical science. A fundamental aspect of their success lies in their size distribution, which governs their behaviour and efficacy in biological environments.
This article examines the significance of lipid nanoparticle size distribution, discussing its effects on nanoparticle performance and detailing the sophisticated methods used to analyze this important feature.
What is Nanoparticle Size Distribution?
Nanoparticle size distribution describes the range and proportion of different sizes of particles present in a sample. This distribution can be characterized by several key metrics, including the mean size and polydispersity index (PDI). The mean size is an average measure of all the particles, while the PDI indicates the degree of size variability within the sample.
The optimal mean size for a lipid nanoparticle can vary depending on the specific composition and formulation method, and can be adapted to the desired application. However, generally, a size range from 50 to 200 nanometers (nm) is considered optimal for most therapeutic applications.
On the other hand, a PDI lower than 0.3 ensures that the lipid nanoparticle formulation has a consistent and uniform size. A low PDI signifies a narrow size distribution, crucial for ensuring consistent behaviour and performance. In contrast, a higher PDI (> 0.3) indicates a broad size distribution with a higher degree of variability in the particle size.
Impact of Size Distribution on Lipid Nanoparticle Performance
The size distribution of lipid nanoparticles affects their physical and chemical stability, ability to encapsulate and release therapeutic agents, and interaction with biological systems and biodistribution. Uniformly sized nanoparticles tend to have predictable pharmacokinetics and biodistribution profiles, which are essential for effective drug delivery. All these properties are also influenced by the composition and surface properties.
For instance, nanoparticles in the size range of 50-200 nm are known to have a prolonged circulation time in the bloodstream [1]. This size range also facilitates the passive targeting of tumor tissues through the enhanced permeability and retention effect, which is crucial for cancer therapies [2].
The cellular uptake of nanoparticles is also highly dependent on their size. Nanoparticles with lower diameter are typically internalized by cells via endocytosis more efficiently than larger particles. This enhanced uptake is essential for the effective delivery of therapeutic agents, including nucleic acids, into target cells [3].
Moreover, the immune response can also be influenced by their size, with smaller nanoparticles generally inducing a weaker immune response compared to larger ones. This aspect is particularly important for the design of nanoparticle-based vaccines and immunotherapies [1].
Size distribution also impacts the stability. Narrow size distribution, indicative of monodisperse systems, are often associated with better stability and reproducibility in therapeutic applications. Conversely, broad size distribution can lead to heterogeneity in particle behaviour, affecting their overall efficacy and safety profile [3].
Techniques for Measuring Lipid Nanoparticle Size Distribution
Several analytical techniques are employed to characterize the size distribution of lipid nanoparticles, each with its advantages and limitations. Dynamic Light Scattering (DLS) is one of the most commonly used methods for this purpose. DLS measures the time-dependent fluctuations in the scattering of light by nanoparticles in suspension, providing information about their hydrodynamic diameter.
The hydrodynamic diameter of a nanoparticle is a measure of the particle’s effective size in a fluid medium, including the surrounding solvation layer and any bound molecules. Unlike the physical diameter, which is the actual distance across the nanoparticle, the hydrodynamic diameter takes into account how the particle interacts with the solvent molecules around it. This technique is valued for its simplicity and rapid measurement capabilities.
Nanoparticle Tracking Analysis (NTA) is another powerful technique that offers high-resolution size distribution data. NTA tracks the Brownian motion of individual nanoparticles in a liquid suspension, allowing for the direct visualization and sizing of particles. This method provides number-based size distributions and can measure particle concentration.
Electron Microscopy (EM), including Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM), provides direct imaging, size measurement, and morphological characterization. CRYOTEM is an additional methodology providing further details of the specific structures.
Atomic Force Microscopy (AFM) is another imaging technique used to measure the size distribution of nanoparticles. AFM uses a mechanical probe to scan the surface of nanoparticles, providing three-dimensional topographical images. This method is advantageous for its ability to measure particle height and provide detailed surface characteristics.
The choice of technique for measuring lipid nanoparticle size distribution depends on several factors, including the required resolution, sample characteristics, and available resources. Combining multiple techniques often provides a more comprehensive understanding of the size distribution, enabling researchers to optimize formulations for specific applications.
Understanding the importance of Size Distribution with DIVERSA’s Technology
The precise control and understanding of the size distribution of lipid nanoparticle is essential for optimizing their performance in drug delivery and vaccine applications.
The importance of this parameter is demonstrated by DIVERSA’s proprietary technology. Data from DLS and NTA characterization shows that DIVERSA’s nanoparticles can be tailored for different sizes, always maintaining a highly uniform size distribution.Our delivery technology also demonstrates significant stability across several biological fluids, as well as efficient intracellular delivery of therapeutic molecules and in vivo efficacy.
Furthermore, our lipid-based nanocarriers demonstrate exceptional loading capacity, effectively associating and delivering a broad spectrum of compounds, including APIs, peptides, proteins, and oligonucleotides. This highlights their remarkable versatility and significant application potential.
With DIVERSA’s customizable approach, our nanoparticle technology can be tailored to incorporate your specific molecules, enhancing their therapeutic potential for specific medical indications.
We offer innovation and expertise to impact the development of innovative therapeutics.
For more detailed information about our technology, visit our web!
References
- Chan, H.W.; Chow, S.; Zhang, X.; Kwok, P.C.L.; Chow, S.F. Role of Particle Size in Translational Research of Nanomedicines for Successful Drug Delivery: Discrepancies and Inadequacies. Journal of Pharmaceutical Sciences 2023, 112, 2371–2384, doi:10.1016/j.xphs.2023.07.002.
- Caputo, F.; Clogston, J.; Calzolai, L.; Rösslein, M.; Prina-Mello, A. Measuring Particle Size Distribution of Nanoparticle Enabled Medicinal Products, the Joint View of EUNCL and NCI-NCL. A Step by Step Approach Combining Orthogonal Measurements with Increasing Complexity. Journal of Controlled Release 2019, 299, 31–43, doi:10.1016/j.jconrel.2019.02.030.
- Mitchell, M.J.; Billingsley, M.M.; Haley, R.M.; Wechsler, M.E.; Peppas, N.A.; Langer, R. Engineering Precision Nanoparticles for Drug Delivery. Nat Rev Drug Discov 2021, 20, 101–124, doi:10.1038/s41573-020-0090-8.
