Cationic amphiphilic drugs self-assemble to the core–shell interface of PEGylated phospholipid micelles and stabilize micellar structure

Abstract

Since polymeric micelles are promising and have potential in drug delivery systems, people have become more interested in studying the compatibility of polymeric carriers and drugs, which might help them to simplify the preparation method and increase the micellar stability. In this article, we report that cationic amphiphilic drugs can be easily encapsulated into PEGylated phospholipid (PEG–PE) micelles by self-assembly method and that they show high encapsulation efficiency, controllable drug release and better micellar stability than empty micelles. The representative drugs are doxorubicin and vinorelbine. However, gemcitabine and topotecan are not suitable for PEG–PE micelles due to lack of positive charge or hydrophobicity. Using a series of experiments and molecular modelling, we figured out the assembly mechanism, structure and stability of drug-loaded micelles, and the location of drugs in micelles. Integrating the above information, we explain the effect of the predominant force between drugs and polymers on the assembly mechanism and drug release behaviour. Furthermore, we discuss the importance of p K a and to evaluate the compatibility of drugs with PEG–PE in self-assembly preparation method. In summary, this work provides a scientific understanding for the reasonable designing of PEG–PE micelle-based drug encapsulation and might enlighten the future study on drug–polymer compatibility for other polymeric micelles.

Production of Fluconazole-Loaded Polymeric Micelles Using Membrane and Microfluidic Dispersion Devices

“…Figure 9 shows the effect of drug loading on the particle size distribution of micelles generated using microfluidic and membrane devices. It can be seen that under all process conditions, drug-loaded micelles were larger than drug-free micelles, which agrees with the results of similar studies [ 24 ].…”

Enhanced Anticancer Therapeutic Delivery to Tumor Microenvironment via Simultaneous Angiogenesis and Tumor Targeting

“…To visualize the actual shape of the micelles, we took the images of BF‐FA‐VGB‐MCs and they exhibit a uniform spherical morphology ( Figure B ) , with a size around 14–20 nm, exactly consistent with the values measure by dynamic light scattering (DLS) (Table ) and the previous report . Based on the previous calculation, there would be four FA and VGB moieties on the surface of each micelle in theory on average.…”

Antiviral activity of cationic amphiphilic drugs

“…Indeed, these pharmacokinetic characteristics, the possibility to have a poor penetration in specific tissues, and differences in viral strains and/or in the genetic background of the studied populations could explain the few in vivo confirmations of the antiviral efficiency of CADs. To improve the delivery of CADs, approaches based on nanocarriers, like phospholipid micelles or PEGylated graphene, have been proposed [100,101]. Unfortunately these delivery systems can have drawbacks, such as the delay of CAD release inside the cells, as well as the longer/higher storage of the compounds in the tissues that might increase the risk of CAD side effects and toxicity [101].…”