生物分析与生物医学杂志

Magnetically Driven Bioreactors as new Tools in Drug Delivery

Abstract

Monia Taranta, Ilaria Naldi, Settimio Grimaldi, Laura Salvini, Pier Paolo Claudio, Francesca Rocchio, Alex F. Munoz, Stefano Prete and Caterina Cinti

The pharmacological properties of many drugs can be improved by drug delivery systems able to drive therapeutic agents to target regions. The use of carriers, in fact, may reduce possible cytotoxic effects of drugs and increase their bioavailability at the site of action, thus improving the efficacy and the safety of treatments. Therefore, we have developed an erythrocyte-based drug delivery system (erythro-magneto-HA virosome), which has the potential to be magnetically guided to specific sites and to fuse with target cells. These engineered erythrocytes have demonstrated in previous work a very high in vitro capability to release anticancer drugs directly inside target cells. Because the erythro-magneto-HA virosomes (EMHVs) proved to be promising carriers, we decided to investigate in more details the effectiveness and safety of this erythrocyte-based drug delivery system.

We evaluated the ability of the EMHVs to be specifically localized in vivo to desired sites by means of an external magnetic field and to protect an anticancer drug such as 5-Aza-2’-deoxycytidine from degradation. Additionally we have assessed the ability of the EMHVs to act as bioreactors and to convert the pro-drug 5-Aza-2’-deoxycytidine into an active drug. Finally, we have studied the interaction of the EMHVs with the host immune system.

The pro-drug 5-Aza-2’-deoxycytidine has short half-life when systemically injected and needs to be phosphorylated to become an active drug. We found that when inside the engineered erythrocytes it is protected by degradation and is transformed in its active form thus becoming readily available for uptake by the targeted cells. Moreover, we have observed that the EMHVs used didn’t cause either a cell-mediated or a humoral immune response in host mice having the same haplotype of the donors.

These findings suggest that erythro-magneto-HA virosomes are a safe and useful drug delivery system that may offer numerous advantages for several clinical applications.