Long‐term Treatment With Autologous Red Blood Cells Loaded With Dexamethasone 21–Phosphate in Pediatric Patients Affected by Steroid‐dependent Crohn Disease

Castro, M.; Rossi, Luigia; Papadatou, B.; Bracci, F.; Knafelz, D.; Ambrosini, M.I.; Calce, Angelica; Serafini, Sonja; Isacchi, G; D’Orio, F.; Mambrini, Giovanni; Magnani, Mauro

doi:10.1097/mpg.0b013e3180320667

Cited by 55 publications

(24 citation statements)

References 24 publications

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“…Similar approach has been tested in the patients with inflammatory bowel disease (IBD, such as Crohn disease) and in this study three repetitive re-infusions of autologous RBC loaded with DEX (every four weeks) also provided a prolonged elevation of DEX blood level, permitting the patients to withdraw previously prescribed poorly tolerated steroids and still achieve remission that has been maintained for several months103. Similar encouraging results have been observed in a study involving 18 pediatric patients treated with monthly infusions of autologous RBC-loaded DEX for two years104. Finally, a very recent randomized controlled study of this treatment in forty IBD patients refractory to conventional steroids showed that by 8 weeks of treatment 75% of twenty patients that received RBC-loaded DEX were in clinical remission (vs 80% in the group that received prednisolone and 10% in the sham group, respectively), but no adverse effects have been detected in RBC-DEX treated group, in contrast with 80% patients showing adverse effects of prednisolone105.…”

Section: Vascular Delivery Of Drugs Encapsulated Into Carrier Rbcsupporting

confidence: 70%

Drug delivery by red blood cells: vascular carriers designed by mother nature

Muzykantov

2010

Expert Opinion on Drug Delivery

346

294

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Importance of the field-Vascular delivery of several classes of therapeutic agents may benefit from carriage by red blood cells (RBC), for example, drugs that require delivery into phagocytic cells and those that must act within the vascular lumen. The fact that several protocols of infusion of RBCencapsulated drugs are been currently explored in patients illustrates a high biomedical importance for the field.Areas covered by this review-Two strategies for RBC drug delivery are discussed: encapsulation into isolated RBC ex vivo followed by infusion in compatible recipients and coupling therapeutics to surface of RBC. Studies of pharmacokinetics and effects in animal models and in human studies of diverse therapeutic enzymes, antibiotics and other drugs encapsulated in RBC are described and critically analyzed. Coupling to RBC surface of compounds regulating immune response and complement, affinity ligands, polyethylene glycol alleviating immune response to donor RBC and fibrinolytic plasminogen activators is d escribed. Also described is a novel, translation-prone approach for RBC drug delivery by injecting of therapeutics conjugated with fragments of antibodies providing safe anchoring of cargoes to circulating RBC, without need for ex vivo modification and infusion of RBC.What the reader will gain-The readers will gain historical perspective, current status, challenges and perspectives of medical applications of RBC for drug delivery.Take home message-RBC represent naturally designed carriers for intravascular drug delivery, characterized by unique longevity in the bloodstream, biocompatibility and safe physiological mechanisms for metabolism. Novel approaches for encapsulating drugs into RBC and coupling to RBC surface provide promising avenues for safe and widely useful improvement of drug delivery in the vascular system.

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Section: Vascular Delivery Of Drugs Encapsulated Into Carrier Rbcsupporting

confidence: 70%

Drug delivery by red blood cells: vascular carriers designed by mother nature

Muzykantov

2010

Expert Opinion on Drug Delivery

346

294

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“…144 The possibility of the translation of the manual encapsulation of drug/nanomaterials in RBCs to the clinical setting is not so far away, considering the availability of a technology that permit to perform automatically the loading procedure and that has been implemented at the industrial level by two European companies, EryDel SpA in Italy (www.erydel.com) 145 and Erythec Pharma in France (www.erytech.com). 146 These companies are specialized in the development of drugs and diagnostics delivered through human red blood cells via a proprietary medical device (to encapsulate the therapeutic agent) that has not yet reached the market, nevertheless clinical trials are ongoing on voluntaries patients for treatment of chronic inflammatory diseases [147][148][149] and neurological diseases. 150 The recent development of SPIO-RBCs constructs could provide superior performance of imaging technologies, such as MRI or combined multimodality imaging, but they could be also useful in new diagnostic applications, such as Magnetic Particle Imaging (MPI) that is a novel realtime imaging technique introduced by Philips.…”

Section: Rbcs For the Encapsulation And Delivery Of Magnetic Nanopartmentioning

confidence: 99%

Red Blood Cells as Carriers of Iron Oxide-Based Contrast Agents for Diagnostic Applications

Antonelli¹,

Magnani²

2014

j biomed nanotechnol

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New biomedical strategies are being developed to improve disease detection, therapeutic monitoring, and treatment efficacy in several contexts for example in anti-angiogenic chemotherapy, and prevention of cardiovascular disorders. The use of contrast agents to improve the sensitivity and resolution of diagnostic imaging modalities, detect lesions or organs, and evaluate organ function was immediately recognized. In the last years, superparamagnetic iron oxide (SPIO) nanoparticles have been clinically used as MRI contrast agents for the diagnosis of liver diseases, due to their ability to shorten T 2 * relaxation times. After the intravenous administration, SPIO nanoparticles are rapidly eliminated from the bloodstream since they are selectively taken up by the Kupffer cells in the liver, spleen, and bone marrow thus improving the clinical tumor detection in these tissues. However, for the investigation of vascular system including functional cardiac diagnosis, angiography and cardiac wall motion assessment, contrast agents with long blood circulation time would be necessary. In fact, imaging applications for long-term monitoring require the repeated administration of SPIO bolus injections, which complicates quantitative comparisons due to the temporal variations in concentration. In this context, researchers have developed several SPIO delivery systems based on red blood cells (RBCs) used as carriers to increase the blood circulation time of contrast agents. Encapsulation of SPIOs into RBCs appears the most attractive strategy to obtain magnetic RBC-constructs suitable for MRI and MPI analyses of blood vascular system.

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“…As an advantage, in the optimum conditions of the loading procedure (using more gentle methods for loading), the life‐span of the resulting carrier cells may be comparable with that of normal erythrocytes [1,6,7] . Erythrocytes have been used as circulating intravenous slow‐release carriers for the delivery of antineoplasm agents, antiparasitic drugs, antiretroviral agents, vitamins, steroids, antibiotics, and cardiovascular drugs among others [1,6–34] …”

Section: Introductionmentioning

confidence: 99%

Preparation and in-vitro characterization of tramadol-loaded carrier erythrocytes for long-term intravenous delivery

Foroozesh

Hamidi

Zarrin

et al. 2011

Journal of Pharmacy and Pharmacology

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Long‐term Treatment With Autologous Red Blood Cells Loaded With Dexamethasone 21–Phosphate in Pediatric Patients Affected by Steroid‐dependent Crohn Disease

Abstract: These data suggest that repeated infusions of RBCs loaded with Dex 21-P can be safe and useful to maintain long-term remission in pediatric patients with moderately active CD.

Cited by 55 publications

References 24 publications

Drug delivery by red blood cells: vascular carriers designed by mother nature

Drug delivery by red blood cells: vascular carriers designed by mother nature

Red Blood Cells as Carriers of Iron Oxide-Based Contrast Agents for Diagnostic Applications

Preparation and in-vitro characterization of tramadol-loaded carrier erythrocytes for long-term intravenous delivery

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