Drug, enzyme and peptide delivery using erythrocytes as carriers

Abstract Erythrocytes are potential biocompatible vectors for different bioactive substances, including drugs. These can be used successfully as biological carriers of drugs, enzymes and peptides. There are currently diverse methods that permit drug encapsulation in erythrocytes with an appropriate yield. The methods most commonly employed are based on a high-haematocrit dialysis procedure, mainly hypo-osmotic dialysis. Erythrocytes loaded with drugs and other substances allow for different release rates to be obtained. Encapsulation in erythrocytes significantly changes the pharmacokinetic properties of drugs in both animals and humans, enhancing liver and spleen uptake and targeting the reticulo-endothelial system (RES). Amongst other applications, erythrocytes have been used for drug-targeting the RES with aminoglycoside antibiotics; the selective transport to certain organs and tissues of certain antineoplastic drugs, such as methotrexate, doxorubicine, etoposide, carboplatin, etc.; the encapsulation of angiotensin-converting enzyme (ACE) inhibitors, systemic corticosteroids, the encapsulation of new prodrugs with increased duration of action, etc. Erythrocytes are also attractive systems in the sense of their potential ability to deliver proteins and therapeutic peptides. Thus, erythrocytes have been used for the transport of enzymes destined for the correction of metabolic alterations as l -asparaginase, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (AlDH) among others. Erythrocytes have been used successfully as carriers of anti-HIV peptides, such as AZT, nucleoside analogues, antisense oligonucleotides, antineoplastic peptides, erythropoietin, interleukin 3, etc. Amongst other applications, mention may be made of paramagnetic erythrocytes, encapsulation of MRI contrast agents or the study of the metabolism of the red cell. Although erythrocytes have been applied with different uses in human medicine, their deployment is still very limited due to difficulties involving storage, its exposure to contamination and the absence of a validated industrial procedure for its preparation.