RESUMO
Several challenges need to be overcome when applying nucleic acids as therapeutic agents. We developed a new way to control the onset of the release of cholesterol-conjugated oligonucleotides with a simple, versatile, and cheap platform. Moreover, we combine the platform into a dual-release system that can release a hydrophobic drug with zero-order kinetics, followed by a rapid release of cholesterol-conjugated DNA.
Assuntos
DNA , Oligonucleotídeos , Emulsões/química , DNA/química , ColesterolRESUMO
There is an increasing demand for transient materials with a predefined lifetime like self-erasing temporary electronic circuits or transient biomedical implants. Chemically fueled materials are an example of such materials; they emerge in response to chemical fuel, and autonomously decay as they deplete it. However, these materials suffer from a slow, typically first order decay profile. That means that over the course of the material's lifetime, its properties continuously change until it is fully decayed. Materials that have a sharp on-off response are self-immolative ones. These degrade rapidly after an external trigger through a self-amplifying decay mechanism. However, self-immolative materials are not autonomous; they require a trigger. We introduce here materials with the best of both, i.e., materials based on chemically fueled emulsions that are also self-immolative. The material has a lifetime that can be predefined, after which it autonomously and rapidly degrades. We showcase the new material class with self-expiring labels and drug-delivery platforms with a controllable burst-release.
RESUMO
Drug delivery systems that release hydrophobic drugs with zero-order kinetics remain rare and are often complicated to use. In this work, we present a gellified emulsion (emulgel) that comprises oil droplets of a hydrolyzable oil entrapped in a hydrogel. In the oil, we incorporate various hydrophobic drugs and, because the oil hydrolyzes with zero-order kinetics, the release of the drugs is also linear. We tune the release period from three hours to 50 h by varying the initial oil concentration. We show that the release rate is tunable by varying the initial drug concentration. Our quantitative understanding of the system allows for predicting the drug release kinetics once the drug's partition coefficient between the oil and the aqueous phase is known. Finally, we show that our drug delivery system is fully functional after storing it at -20 °C. Cell viability studies show that the hydrolyzable oil and its hydrolysis product are non-toxic under the employed conditions. With its simplicity and versatility, our system is a promising platform for the zero-order release of the drug.