Abstract
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.
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References
Barker SA, Khossravi D . Drug delivery strategies for the new millenium Drug Discov Today 2001 6: 75–77
Flott TR . Recombinant adeno-associated virus vectors for cystic fibrosis gene therapy Curr Opin Mol Ther 2001 3: 497–502
Cui FD et al. Highly efficient gene transfer into murine liver achieved by intravenous administraton of naked Epstein–Barr virus (EBV)-based plasmid vectors Gene Therapy 2001 8: 1508–1513
Jayan GC et al. SV-40-derived vectors provide effective transgene expression and inhbition HIV-using constitutive, conditional, and pol III promotors Gene Therapy 2001 8: 1033–1042
Klimatcheva E et al. Defective lentiviral vectors are efficiently trafficked by HIV-1 and inhibitor replication Mol Ther 2001 3: 928–939
Schwartz JJ, Zhang S . Peptide-mediated cellular delivery Curr Opin Mol Ther 2000 2: 162–167
Juliano RL, Yoo H . Aspects of the transport and delivery of antisense oligonucleotides Curr Opin Mol Ther 2000 2: 297–303
Vyas SP, Singh A, Sihorkar V . Ligand-receptor-mediated drug delivery: an emerging paradigm in cellular drug targeting Crit Rev Ther Drug Carrier Syst 2001 18: 1–76
Russell-Jones GJ . Use of vitamin B12 conjugates to deliver protein drugs by the oral route Crit Rev Ther Drug Carrier Sys 1998 15: 557–586
Reddy JA, Low PS . Folate-mediated targeting of theraputic and imaging agents to cancer Crit Rev Ther Drug Carrier Sys 1998 15: 587–627
Becker A et al. Receptor-targeted optical imaging of tumors with near-infrared fluorescent ligands Nature Biotech 2001 19: 327–331
Magnani M et al. Erythrocyte engineering for drug delivery and targeting Biotechnol Appl Biochem 1998 28: 1–6
Rossi L et al. Erythrocyte-mediated delivery of dexamethasone in patients with chronic obstructive pulmonary disease Biotech Appl Biochem 2001 33: 85–89
Magnani M et al. Targeting antiretroviral nucleoside analogues in phosphorylated form to macrophages: in vitro and in vivo studies Proc Natl Acad Sci USA 1992 89: 6477–6481
Chiarantini L, Rossi L, Fraternale A, Magnani M . Modulated red blood cell survival by membrane protein clustering Mol Cell Biochem 1995 144: 53–59
Franchetti P et al. A new acyclic heterodinucleotide active against human immunodeficienct virus and herpes simplex virus Antivir Res 2000 47: 149–158
Rossi L et al. Erythrocyte-mediated delivery of a new homodinucleotide active against human immunodeficiency virus and herpes simplex virus J Antimicrob Chem 2001 47: 819–827
Magnani M et al. Targeting antiviral nucleotide analogues to macrophages J Leukocyte Biol 1997 62: 133–137
Antonelli A et al. Efficient inhibition of macrophage TNF-α production upon targeted delivery of K48R ubiquitin Br J Haematol 1999 104: 475–481
Acknowledgements
This work was partially supported by Project AIDS 1999, PRIN Project and Target Project on Biotechnology of CNR. We are indebted to Dr Massimo Castro, Vincenzina Lucidi and Francesco D'Orio from Hospital ‘Bambin Gesù’ in Rome for the studies on CF patients.
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Magnani, M., Rossi, L., Fraternale, A. et al. Erythrocyte-mediated delivery of drugs, peptides and modified oligonucleotides. Gene Ther 9, 749–751 (2002). https://doi.org/10.1038/sj.gt.3301758
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DOI: https://doi.org/10.1038/sj.gt.3301758
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