Enhanced Control of Liposomal Drug Release by Drug–Aptamer Complexes

Conventional diffusion-controlled drug delivery systems (DDS) can have undesirable initial burst release, leading to potential systemic toxicity, and the rate of basal release can deplete content, shortening the duration of effect. Here, it is hypothesized that conventional drug delivery systems-using liposomes as an example-can be enhanced by incorporation of an aptamer that binds specifically to the encapsulated drug. Affinity of the aptamer to the drug within liposomes (Lipo-Apt) would slow release. It is demonstrated that this approach works with a range of relatively small and hydrophilic molecules, including tetrodotoxin (TTX), serotonin (Ser), and kanamycin (Kan). The in vivo utility of this system in providing prolonged local anesthesia with TTX injected at the sciatic nerve in rats is further demonstrated. A single injection of TTX-loaded Lipo-Apt results in 6.6 d of nerve blockade, a fourfold improvement over the duration achieved by liposomes without aptamers, and 26-fold over the aptamer-drug complex. In part, the improved efficacy of Lipo-Apt is also due to slower release reducing systemic toxicity, which allows delivery of larger drug doses. These studies demonstrate that Lipo-Apt is a promising approach to enhancing control of release of drugs by DDS, reducing toxicity and enhancing duration of effect.