Note: Most of the content in this article is drawn from the referenced literature, titled “Lipid Nanoparticles for Drug Delivery.” For a more in-depth understanding, please consult the original paper. The original article can be accessed at: https://onlinelibrary.wiley.com/doi/epdf/10.1002/anbr.202100109

　　Lipid nanoparticles (LNPs) exhibit excellent biocompatibility, biodegradability, and encapsulation efficiency, making them ideal carriers for nucleic acids such as DNA, mRNA, and siRNA. In this article, the authors provide a detailed overview of LNP preparation, characterization, and applications across multiple chapters. Subsequently, the author highlights key points, focusing on LNP characterization and their use in encapsulating hydrophobic drugs.

　　1. Characterization of LNP

　　Particle size, ZP, and surface morphology

　　The average particle size of LNP typically falls within the 100–400 nm range; when administered systemically via intravenous injection, a particle size of 10–150 nm is more desirable. Furthermore, the polydispersity index (PDI) reflects the breadth of the particle-size distribution, and both PDI and particle size can be measured simultaneously using a laser particle sizer. A PDI below 0.2 generally indicates a narrow particle-size distribution; however, a PDI in the range of 0.2–0.3 may still be acceptable to some researchers.

　　ZP refers to the surface zeta potential of particles, as measured by a Zeta Potential Analyzer. When the absolute value of ZP exceeds 30 mV, the particles are generally considered sufficiently repulsive to maintain electrostatic stability. However, for systemic drug delivery, it is advisable to select particles with near-neutral charge; such near-neutral charges result in weak repulsive interactions, which also account for the increase in particle size observed during LNP storage.

　　Scanning electron microscopy (SEM), atomic force microscopy (AFM), and transmission electron microscopy (TEM) can all be used to examine the surface morphology of particles. TEM and SEM provide morphological information by analyzing electrons transmitted through the particle’s internal structure and its surface, respectively; in contrast, AFM enables the acquisition of three-dimensional topographical features of LNPs.

　　Determination of Encapsulation Efficiency (EE)

　　Encapsulation efficiency is a key metric for LNP formulations, reflecting the utilization efficiency of the active ingredient. Factors such as lipid type, composition, crystallinity, and drug solubility can all influence encapsulation efficiency. Speaking of crystallinity, this concept may be less familiar to readers: lipids and encapsulated drugs can undergo polymorphic transitions during storage, leading to drug instability or loss, thereby affecting both drug loading and release kinetics. Typically, differential scanning calorimetry (DSC) and X-ray diffraction (XRD) are employed in conjunction to determine the crystallinity of the sample.

　　2. Encapsulation of hydrophobic drugs

　　LNP‑mediated nucleic acid encapsulation has been extensively discussed in previous posts, and Mingtai’s microfluidic devices have already provided researchers with a wide range of such services. Given that nucleic acids are hydrophilic, can LNPs also be used to encapsulate hydrophobic drugs? The answer is yes. In fact, 90% of drugs currently under development are hydrophobic, making the development of delivery systems for these compounds an urgent priority.

　　LNP has been widely employed for the delivery of hydrophobic drugs. For instance, docetaxel (DTX), a potent antitumor and antiangiogenic agent, is limited in clinical use due to its poor water solubility and high cytotoxicity. To address these challenges, DTX‑loaded LNPs were prepared using Compritol 888 ATO as the lipid matrix and Pluronic F127 and Span 80 as stabilizers. Characterization revealed that the LNPs exhibited a particle size of 128 nm, a PDI of 0.2, an encapsulation efficiency (EE) of 86%, and a drug loading (DL) of 2%. Moreover, a sustained‑release profile was observed, and notably, the DTX‑loaded LNPs remained stable over a period of 120 days.

　　The paper also discusses the encapsulation of various other hydrophobic drugs using LNP; while some of these encapsulations did not employ microfluidic techniques, among the researchers I have recently consulted, there are indeed cases where microfluidics was used to encapsulate traditional Chinese medicine powders. Since these powders are hydrophobic, they were dissolved in an ethanol phase, with PBS buffer serving as the aqueous phase; through careful formulation optimization, uniformly sized and stable nanoparticles were ultimately obtained.

　　In summary, the characterization of LNP formulations is an indispensable step following encapsulation; it essentially provides a quantitative assessment of particle morphology. By leveraging these quantitative parameters, we can more effectively elucidate the relationship between lipid structure and function. Against the backdrop of the burgeoning research on RNA vaccines, microfluidic technology has increasingly been focused on the encapsulation of nucleic acid therapeutics; however, its applications extend far beyond this domain. As research into the encapsulation of hydrophobic drugs continues to advance, microfluidic technology is poised to assume an even more prominent role in the encapsulation of a wide array of drug types.

　　References:

　　1.L.Xu,X.Wang,G.Yang,et al.,Lipid Nanoparticles for Drug Delivery.Adv.NanoBiomed Res.2022,2,2100109.

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