Encapsulating Active Pharmaceutical Ingredients in Self-Assembling Adamantanes with Short DNA Zippers.

Abstract

Formulating pharmaceutically active ingredients for drug delivery is a challenge. There is a need for new drug delivery systems that take up therapeutic molecules and release them into biological systems. We propose a novel mode of encapsulation that involves matrices formed through co‐assembly of drugs with adamantane hybrids that feature four CG dimers as sticky ends. Such adamantanes are accessible via inexpensive solution‐phase syntheses, and the resulting materials show attractive properties for controlled release. This is demonstrated for two different hybrids and a series of drugs, including anticancer drugs, antibiotics, and cyclosporin. Up to 20 molar equivalents of active pharmaceutical ingredients (APIs) are encapsulated in hybrid materials. Encapsulation is demonstrated for DNA‐binding and several non‐DNA binding compounds. Nanoparticles were detected that range in size from 114–835 nm average diameter, and ζ potentials were found to be between −29 and +28 mV. Release of doxorubicin into serum at near‐constant rates for 10 days was shown, demonstrating the potential for slow release. The encapsulation and release in self‐assembling matrices of dinucleotide‐bearing adamantanes appears to be broadly applicable and may thus lead to new drug delivery systems for APIs.