The extracellular and intracellular barriers seriously affect the delivery of RNA-based drugs, limiting the success of RNA clinical applications. Similarly, mRNA-based therapies require a delivery vehicle to protect the mRNA from nucleases and promote cellular uptake and release into the cytoplasm. Polymeric micelles represent a powerful, versatile nanotherapeutic platform that can be used to deliver RNA-based drugs. At present, many types of copolymers have been used for micelle formation and can be easily functionalized to improve the pharmacokinetics of RNA-based drugs.
Micelleplexes have the same characteristics as polymeric micelles. They are composed of amphiphilic polymers (diblock, triblock or graft copolymers). In an aqueous environment, they can self-assemble into a micelle structure composed of a hydrophilic shell and hydrophobic core. Hydrophobic core forms the microenvironment of hydrophobic drug binding through hydrophobic interaction, while hydrophilic corona-forming components of polymer micelles often interfere with RNA binding. In turn, the hydrophilic corona is responsible for stabilizing micelles in the plasma and preventing phagocytosis/conditioning by minimizing non-specific interactions with biological components.
Fig.1 Schematic illustration of the micelleplexes. CMC: critical micelle concentration. (Pereira, 2017)
Because of their favorable properties, such as the capacity to effectively solubilize various poorly soluble drugs, biocompatibility, longevity, high stability in vivo and in vitro, and their ability to accumulate in pathological areas with damaged blood vessels, micelleplexes have gained great popularity. Besides, by engineering the surface of micelles with various ligands and cells, the micelles have specific targeting and intracellular aggregation, which endows them with additional functions.
As mentioned above, the composition and structure of micelleplex system, including its surface modification, have an important influence on its stability and biological interaction, especially in drug absorption, drug oral bioavailability, internalization of receptor-mediated endocytosis and drug delivery pathway in the bloodstream.
Fig.2 Functions of micelleplex. (Pereira-Silva, 2020)
Micelleplex, as an active targeting drug delivery system in the pharmaceutical industry, has attracted great attention in the past decades, Creative Biolabs is no exception. After years of continuous exploration and summary, we have made some progress in the development of micelleplex for mRNA delivery.
We can optimize the micelleplex structure system according to different project requirements, improve the mRNA-based drug delivery system, and successfully target cells/tissues/organs in a time- and cost-effective manner, while ensuring silence, correcting or introducing specific genes with minimum adverse reactions.
We are optimistic that more and more delivery systems based on RNA drugs will make progress through clinical development and will become part of the approved treatment in the next few years. Creative Biolabs actively seizes the opportunity to spare no effort to provide customized micelleplex synthesis and production for mRNA delivery to meet customers' demands. If you are interested in our services, please feel free to contact us.