Quality Control of Liposomes

The use of nanostructured components in drug manufacturing and, more specifically, targeted drug delivery have recently become a major pharmaceutical trend. Nanodrugs include a series of pharmaceutical preparations, including dendrimers, nanocrystals, micelles, liposomes and polymer nanoparticles. Among them, liposomes are the most studied nanoparticles and effective drug carriers. The preparation and production of liposomes include various steps. The more complex their structure is, the more process control and quality attributes need to be monitored.

Background of Liposomal Quality Control

It is well known that small changes in liposome formulations may significantly affect clinical outcomes, such as pharmacokinetics and pharmacodynamics. Kapoor et al. proposed the influence of critical quality attributes (CQAs) on the in vivo performance of liposomes by reviewing the liposome products submitted for approval. The CQA of liposome products was characterized, including various tests, such as particle size, particle size distribution, lipid impurities, in vitro drug release, lamellarity, free and entrapped drug ratio, etc.

=" Fig.1 Formulation analysis and characterization.

Importance of Quality Control Evaluation

The characterization and quality control of liposomes is the fatal weakness of liposome production to a certain extent. Aqueous loading is controlled by physical and structural parameters, such as size, shape and number of lamellae, which control the capture volume of aqueous. In order to optimize the loading capacity of liposomes, the hydration medium should be well controlled and defined, and the exact composition and pH value of the size reducing medium and storage medium should be well defined.

Table 1 Major liposome-specific characteristics. (Lee, 2020)

Details of Liposomal Quality Control

As shown in Table 1, the study of liposomes includes several main characteristics of liposomes.

• Basic Characteristics

Particle size and particle size distribution are the key factors in regulating pharmacokinetics of liposomes. Dynamic light scattering (DLS) is a commonly used technique for measuring particle size and size distribution. In addition, the morphology can be evaluated by electron microscopy to provide additional information about particle size and lamellarity.

In recent years, various kinds of microscopy have been applied to the visualization of liposomes, including polarization microscopy, fluorescence microscopy and various electron microscopy methods, such as transmission, freezing, freeze fracture and environmental scanning electron microscopy.

• Encapsulation Efficiency and Release Rate

The release of liposomes in vitro should be carried out in an appropriate simulated physiological medium. In vitro release is crucial for understanding the in vivo behavior of the product, because the encapsulated liposome drug may exhibit significantly different in vivo behavior from the released free drug. Scientists encourage the establishment of stereoscopic in vitro correlations to justify the use of in vitro release tests to predict in vivo performance. Under the same conditions, the formula with the highest entrapment efficiency was optimized by measuring the entrapment efficiency.

• Physical Stability

Liposomes are thermodynamically unstable, so they are prone to fusion or aggregation during storage. In most cases, the stability of liposomes is evaluated by the change of particle size. Researchers suggested that the chemical stability of liposomes should also be evaluated. In addition, most liposome researchers evaluate the surface charge by measuring zeta potential to understand liposome-liposome and liposome-membrane interactions. Charged liposomes can be prepared by adding anionic or cationic molecules to the membrane components of liposomes, or coating charged polymers on the surface of liposomes. Charged liposomes can stabilize the fusion or aggregation of liposomes by electrostatic repulsion.

The reason for the slow development of mass production of liposomes is related to the time spent in solving technical and quality control problems. As a professional liposome development company, Creative Biolabs provides comprehensive quality control analysis and testing services. For more details about our services, please directly contact us.

For Research Use Only. Not For Clinical Use