Erythrocyte-mediated delivery of drugs, peptides and modified oligonucleotides.
An important determinant for the success of every new therapy is the ability to deliver the molecules of interest to the target cells or organ. This selective delivery is even more complex when the therapeutic agents are peptides, modified oligonucleotides or genes. In this paper we summarize the possibility of using autologous erythrocytes for the delivery and targeting of new and conventional therapeutics. In fact, a number of macromolecules can be encapsulated by different procedures into human erythrocytes. These modified cells can then be re-infused into the same or a compatible recipient where they can circulate for several weeks. However, drug-loaded erythrocytes can also be modified to be selectively recognized by tissue macrophages. These phagocyte cells recognize the modified drug-loaded erythrocytes which are able to release their content into the macrophage. The feasibility and safety of the use of erythrocytes as drug delivery systems was evaluated in 10 cystic fibrosis patients, where a sustained release of corticosteroids from dexamethasone 21-phosphate-loaded erythrocytes was obtained. In vitro human erythrocytes were found to be able to deliver ubiquitin analogues and modified oligonucleotides to macrophages. Thus, drug-loaded erythrocytes are safe and useful carriers of new and conventional therapeutics and can be advantageous delivery systems for new clinical applications where proteins and oligonucleotides are therapeutic agents.
Magnani
M
M
Institute of Biochemistry 'Giorgio Fornaini', University of Urbino, Italy. magnani@uniuzb.it
Rossi
L
L
Fraternale
A
A
Bianchi
M
M
Antonelli
A
A
Crinelli
R
R
Chiarantini
L
L
D003550:Cystic Fibrosis / Q000628:therapy*; D003907:Dexamethasone / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D004912:Erythrocytes / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods*; D006207:Half-Life; D006801:Humans; D008264:Macrophages / Q000502:physiology; D009841:Oligonucleotides; D029424:Pulmonary Disease, Chronic Obstructive / Q000628:therapy; D011994:Recombinant Proteins
D009841:Oligonucleotides; D011994:Recombinant Proteins; C004180:dexamethasone 21-phosphate; D003907:Dexamethasone