Lipid-based nanocarriers are used to enhance the bioavailability of poorly-soluble drugs by encapsulating both lipophilic and hydrophilic molecules. Their physical properties, including particle size and polydispersity index (PDI), significantly affect their safety, stability, efficacy, and in vitro/in vivo behavior. Particle size and PDI are critical for the clinical application of nanocarriers, influencing their ability to target specific cells or tissues, drug release, and therapeutic outcomes. Common lipid-based nanocarriers include liposomes, nanoliposomes, vesicular phospholipid gels, solid lipid nanoparticles, transfersomes, and tocosomes. Analytical techniques such as dynamic light scattering (DLS), flow cytometry, and nanoparticle tracking analysis (NTA) are used to characterize these systems. Particle size is crucial for drug delivery, as smaller particles can penetrate tissues more effectively and have better bioavailability. For example, nanocarriers smaller than 150 nm can extravasate into tumors, enhancing drug delivery. In pulmonary delivery, smaller particles are more likely to reach the alveolar region. In transdermal delivery, nanocarriers with sizes between 10–210 nm can penetrate the skin more effectively. For brain delivery, nanocarriers with sizes around 100 nm can cross the blood-brain barrier. The PDI, which measures the uniformity of particle size distribution, is also important for ensuring consistent performance and stability of nanocarriers. A PDI below 0.3 is generally considered acceptable for lipid-based nanocarriers. Various analytical methods are used to determine particle size and PDI, each with its own advantages and limitations. The size and PDI of nanocarriers are essential for their clinical application, as they affect drug delivery efficiency, safety, and therapeutic outcomes. Regulatory agencies require standardized methods for evaluating these parameters to ensure the quality and safety of nanocarriers. Overall, controlling particle size and PDI is crucial for the successful development and clinical application of lipid-based nanocarriers.Lipid-based nanocarriers are used to enhance the bioavailability of poorly-soluble drugs by encapsulating both lipophilic and hydrophilic molecules. Their physical properties, including particle size and polydispersity index (PDI), significantly affect their safety, stability, efficacy, and in vitro/in vivo behavior. Particle size and PDI are critical for the clinical application of nanocarriers, influencing their ability to target specific cells or tissues, drug release, and therapeutic outcomes. Common lipid-based nanocarriers include liposomes, nanoliposomes, vesicular phospholipid gels, solid lipid nanoparticles, transfersomes, and tocosomes. Analytical techniques such as dynamic light scattering (DLS), flow cytometry, and nanoparticle tracking analysis (NTA) are used to characterize these systems. Particle size is crucial for drug delivery, as smaller particles can penetrate tissues more effectively and have better bioavailability. For example, nanocarriers smaller than 150 nm can extravasate into tumors, enhancing drug delivery. In pulmonary delivery, smaller particles are more likely to reach the alveolar region. In transdermal delivery, nanocarriers with sizes between 10–210 nm can penetrate the skin more effectively. For brain delivery, nanocarriers with sizes around 100 nm can cross the blood-brain barrier. The PDI, which measures the uniformity of particle size distribution, is also important for ensuring consistent performance and stability of nanocarriers. A PDI below 0.3 is generally considered acceptable for lipid-based nanocarriers. Various analytical methods are used to determine particle size and PDI, each with its own advantages and limitations. The size and PDI of nanocarriers are essential for their clinical application, as they affect drug delivery efficiency, safety, and therapeutic outcomes. Regulatory agencies require standardized methods for evaluating these parameters to ensure the quality and safety of nanocarriers. Overall, controlling particle size and PDI is crucial for the successful development and clinical application of lipid-based nanocarriers.