Nano-drug carriers include lipid nanoparticles, virus nanoparticles, inorganic nanoparticles, macromolecular nanoparticles, etc. Among them, lipid nano-drug (mainly containing liposomes, solid lipid nanoparticles, phospholipid micelles and cell-secreting vesicles, etc.) has fine stability, excellent drug loading capacity and biocompatibility. It has shown good application prospects in targeted drug delivery, sustained and controlled drug release, improving bioavailability of insoluble drugs and peptide drugs, reducing drug toxic and side effects, etc. Lipid nano-drug is currently the most * approved drug delivery system in clinical practice.
Rapid and accurate characterizations of nanoparticle size, distribution, particle concentration, and zeta potential are essential to accelerate the preparation process of lipid nano-drugs and to ensure the efficacy of clinical applications. Due to the high heterogeneity of lipid nano-drugs, the only way to reveal individual differences masked by centralized averaging and to obtain statistically representative trait distributions is to rapidly analyze nano-drugs one by one on a “single particle” level. However, the small size and fragile structure of lipid nano-drugs make it challenging to quantify them at the single-particle level with multiple parameters.
Fig. 1 (Analysis of the structure and particle size of liposomes)
The existing commercial single-particle characterization techniques are not yet able to meet the needs of lipid nano-drug characterization in terms of sensitivity, resolution, analytical speed, or multiparameter characterization. They are also easily influenced by surrounding environment, while suffering from complicated operation and sample preparation, and extremely expensive instrumentation. Therefore, the development of a fast, sensitive, and high-throughput quantitative characterization technique at the single-particle level is crucial for the R&D and application of lipid nano-drugs. Nanocoulter I particle size analyzer is a “single-particle” detection technology for rapid analysis of cells and nanoparticles in liquid phase. It has the advantages such as rapid, multi-parameter and quantitative detection. However, the traditional Coulter instrument can only be used to detect signals with a particle size larger than 1000 nm due to the limitation of detection range. While the particle size of nano-drug carrier particles is generally less than 200 nm, traditional Coulter instrument cannot perform well in the detection of lipid nano-drugs. Combined with Coulter Principle, Nanocoulter I equipped with photo-etched biochip technology pushes the upper and lower detection limits of nanoparticles to 500 nm and 40 nm respectively, and the sensitivity is several orders of magnitude higher than that of the traditional Coulter instrument; In the field of analysis, the detection of “nano-single particles” is realized. The world’s leading high-precision hypersensitive biological detection platform is created; The development of bio-drugs, especially nano-drugs and vaccines, requires more precise and sensitive assays for characterization.
(Coulter Principle) (Software testing process)
Nanocoulter Ⅰ can achieve high resolution characterization of each particle size by single particle counting of nanoparticles, with a detection rate of up to 5000 particles per minute, and it takes only a few minutes to obtain the test results that take hours to obtain by SEM. In addition, the simultaneous detection of particle concentrations enables the multi-parameter quantitative characterization of individual nanoparticle biochemical traits and the correlation analysis between each parameter. Based on the excellent high resolution, sensitivity, detection speed and multi-parameter characterization capability of Nanocoulter I, this paper established a method for rapid analysis of multiple lipid nano-drugs at the single-particle level, and realized the multi-parameter quantitative characterization of particle size, particle concentration and zeta potential of lipid nano-drugs, which provides a rapid, efficient and practical characterization method for the synthesis optimization, quality control and clinical application of lipid nano-drugs.
(Test experiment report)
The subtle differences between samples with and without the addition of surface-active liposomes are only visible by Nanocoulter I particle size analyzer with the advantages of high precision and single particle detection.
