Preclinical developments of enzyme-loaded red blood cells

Therapeutic enzymes are currently used in the treatment of several diseases. In most cases, the benefits are limited due to poor in vivo stability, immunogenicity, and drug-induced inactivating antibodies. A partial solution to the problem is obtained by masking the therapeutic protein by chemical modifications. Unfortunately, this is not a satisfactory solution because frequent adverse events, including anaphylaxis, can arise.

Among the delivery systems, we focused on red blood cells for the delivery of therapeutic enzymes. Erythrocytes possess a long circulation time, a reduced immunogenicity, there is no need of chemical modifications and the encapsulated enzyme remains active because it is protected by the cell membrane. Here we discuss some representative applications of the preclinical developments of the field. Some of these are currently in clinic, others are approaching the clinic and others are illustrative of the development process. The selected examples are not always the most recent, but they are the most useful for a comparative approach.

The results discussed confirm the central role that red blood cells can play in the treatment of several conditions and suggest the benefit in using a natural cellular carrier in terms of pharmacokinetic, biodistribution, safety, and efficacy.