Mauro Magnani "Drug delivery mediata dagli eritrociti" - 8 giugno 2017 ore 17.00

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 Prof. Mauro Magnani, ordinario di Biochimica, Dipartimento di Scienze Biomolecolari, Università di Urbino.



"Drug delivery mediata dagli eritrociti"

 "Red Blood Cells-mediated drug delivery"

Red blood cells (RBC) are ideally suited to perform as delivery systems having properties that define most of the wanted characteristics of drugs, theranostics and diagnostics carriers.1 These carriers, initially explored for the administration of enzymes to patients with genetic defects, have been shown to be able to carry peptides, proteins, small molecules, nucleic acids, antibodies and a large number of nanomaterials. Carrier RBC during the years have moved from academia to industry and are now actively investigated in several clinical trials and will soon be approved by regulatory agencies. Most of the applications developed involve the transient opening of RBC under controlled condition, the encapsulation of desired agent(s) and the subsequent resealing.2,3 The resulting drug-loaded RBC are then administered to a patient in need. However, RBC can be engineered also by coupling agents on their external surface (proteins, antibodies, peptides, nanoparticles) for targeting to selected districts or exposed molecular targets on the vascular endothelia. Targeting of drug-loaded RBC can be obtained also by inducing red cell membrane modifications that mimic the exposition of a red cell senescence antigen which is known to result in red cell removal from circulation by tissue macrophages. RBC can also be engineered as antigen delivery systems and/or as immunomodulatory agents to induce tolerance. RBC can be engineered also for the encapsulation of a large number of nanomaterials useful in diagnostic applications, especially in the visualization of the vascular system by fluorescent techniques or MPI and MRI.4

In this presentation I will focus on the key properties of RBC that can be advantageously used to engineer new carriers for drugs and diagnostic agents. Special attention will be provided to RBC used as circulating carriers for the delivery of Dexamethasone to be administered to patients in need, and specifically to patients suffering from the rare disease Ataxia telangiectasia. An erythrocyte-based delivery system able to carry out a slow and sustained release of dexamethasone into the bloodstream has been developed and validate by EryDel. This system, consisting of a dedicated medical device, encapsulates the pro-drug dexamethasone sodium phosphate (DSP) into the patient’s erythrocytes, where it is slowly converted to dexamethasone. The erythrocytes are then re-infused into the patient, and the dexamethasone is released into his/her bloodstream for approximately 30 days or more. Thus, the treatment is repeated every three to four weeks. 6-month-phase II study showed improvement of ataxia in AT patients as result of repeated infusions of autologous erythrocytes loaded with dexamethasone. Dexamethasone delivered by erythrocytes proved to be safe and well-tolerated; no side effect usually associated with steroid treatment was observed. Based on this information a Phase 3 clinical trial is ongoing

Selected references:

  1. Pierigè F, Bigini N, Rossi L, Magnani M. Reengineering red blood cells for cellular therapeutics and diagnostics. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2017 Jan 24. doi: 10.1002/wnan.1454. Approaches to erythrocyte-mediated drug delivery.
  2. Rossi L, Pierigè F, Antonelli A, Bigini N, Gabucci C, Peiretti E, Magnani M. Engineering erythrocytes for the modulation of drugs' and contrasting agents' pharmacokinetics and biodistribution. Adv Drug Deliv Rev 2016, pii: S0169-409X(16)30150-8. doi: 10.1016/j.addr.2016.05.008.
  3. Magnani M, Rossi L. Expert Opin Drug Deliv. 2014 May;11(5):677-87. doi: 10.1517/17425247.2014.889679.
  4. Magnani M, Serafini S, Fraternale A, Antonelli A, Biagiotti S, Pierigè F, Sfara C, Rossi L, Red blood cell-based delivery of drugs and nanomaterials for therapeutic and diagnostic applications, in: H.S. Nalwa (Ed.), Encyclopedia of Nanoscience and Nanotechnology 2011, pp. 309-354.