Immunological Response to L-Asparaginase Loaded into Red Blood Cells

Ktavtzoff, Roger; Desbois, Isabelle; Doînel, C.; Colombat, Philippe; Lamagnere, J. P.; Chassaigne, M; Ropars, C.

doi:10.1007/978-1-4615-3030-5_21

Cited by 12 publications

(10 citation statements)

References 7 publications

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“…l-Asparaginase entrapped in red blood cells was quite stable and had markedly prolonged in vivo half-life [69,70]. Intravenous infusion in mice resulted in effective elimination of l-asparaginase for a period of 2 weeks [71], however the immunogenicity of the enzyme seems to be only slightly diminished [72]. Palmitoyl l-asparaginase, another chemically modified derivative of the enzyme encapsulated in liposome, has also been studied in animals [73]; it exhibited about 10-fold prolongation in half-life without acute toxicity.…”

Section: Modified Enzymementioning

confidence: 99%

Pharmacological and clinical evaluation of l-asparaginase in the treatment of leukemia

Narta

Kanwar

Azmi

2007

Critical Reviews in Oncology/Hematology

323

229

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Section: Modified Enzymementioning

confidence: 99%

Pharmacological and clinical evaluation of l-asparaginase in the treatment of leukemia

Narta

Kanwar

Azmi

2007

Critical Reviews in Oncology/Hematology

323

229

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“…In the last three decades, significant efforts have been invested in order to prove the validity of this paradigm and establish clinically applicable strategies for RBC carriage of drugs. RBC are been tested for drug delivery in numerous animal4,12–14 and human studies14. Certain challenges and limitations of using RBC as drug carriers have been identified in these studies.…”

Section: Introduction: Red Blood Cells As Carriers For Drug Deliverymentioning

confidence: 99%

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

Muzykantov

2010

Expert Opinion on Drug Delivery

331

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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“…Formate dehydrogenase Methanol intoxication [264] Cyanide sulfurtransferase (rhodanase) Cyanide intoxication [65][66][67][68][69][70]265,266] Catalase, PEG-catalase Antioxidant [267] l-Asparaginase Antitumor therapy [16,22,24,[83][84][85][86]237,[268][269][270][271][272][273][274][275][276][277][278][279][280][281][282][283][284] l-Methioninase [87,88,285,286] Arginine deiminase [89,90] Hexokinase, glucose oxidase To decrease blood glucose (diabetes) [287,288] Insulin [138][139][140]289,290] Inositol hexaphosphate (IHP) Sickle...…”

Section: Active Substance Application Referencesmentioning

confidence: 99%

Erythrocytes as Carriers: From Drug Delivery to Biosensors

et al. 2020

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Drug delivery using natural biological carriers, especially erythrocytes, is a rapidly developing field. Such erythrocytes can act as carriers that prolong the drug's action due to its gradual release from the carrier; as bioreactors with encapsulated enzymes performing the necessary reactions, while remaining inaccessible to the immune system and plasma proteases; or as a tool for targeted drug delivery to target organs, primarily to cells of the reticuloendothelial system, liver and spleen. To date, erythrocytes have been studied as carriers for a wide range of drugs, such as enzymes, antibiotics, anti-inflammatory, antiviral drugs, etc., and for diagnostic purposes (e.g., magnetic resonance imaging). The review focuses only on drugs loaded inside erythrocytes, defines the main lines of research for erythrocytes with bioactive substances, as well as the advantages and limitations of their application. Particular attention is paid to in vivo studies, opening-up the potential for the clinical use of drugs encapsulated into erythrocytes.Pharmaceutics 2020, 12, 276 2 of 44 property of RBCs allows to load them with biologically active substances of different molecular weights. For these reasons, erythrocytes are promising biocompatible cells for drug delivery.The methods for incorporating various substances into red blood cells differ in the way that substances penetrate the cells. The cause of permeability may be the pores' formation in the cell membrane due to a physical exposure (high voltage electric pulse [10,11] or ultrasound [12]). Drug molecules can also enter the RBCs by endocytosis in the presence of certain chemical compounds (for example, primaquine [13], vinblastine, chlorpromazine, hydrocortisone or tetracaine [14,15]), or using the cell-penetrating peptides bounded to the compound that should be encapsulated [16]. However, the most popular are different variants of osmotic methods.In some cases, RBCs are first exposed to a hyperosmotic pulse of a low molecular weight substance that penetrates very well through the cell membrane (for example, dimethyl sulfoxide (DMSO) [17,18] or glucose [19,20]). After washing the cells, which decreases the external concentration of these compounds and creates a gradient of their concentration between both sides of the RBC membrane, the target drug is introduced into the external volume. Water with this drug begins to enter into the cells to decrease the osmotic pressure there. The process ends when the gradient of DMSO or glucose disappears. The pores close and part of the drug remains into RBCs. Other, the most popular of the osmotic methods are hypoosmotic. These methods are based on creating a hypotonic environment around RBCs, which causes swelling of the cells and opening pores in the cellular membrane, through which therapeutic compounds can penetrate RBCs. Then, a hypertonic solution is introduced into the cell suspension. The pores close, the cells restore their original size, trapping the drug molecules inside the cell. Osmotic methods are divided into severa...

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Immunological Response to L-Asparaginase Loaded into Red Blood Cells

Cited by 12 publications

References 7 publications

Pharmacological and clinical evaluation of l-asparaginase in the treatment of leukemia

Pharmacological and clinical evaluation of l-asparaginase in the treatment of leukemia

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

Erythrocytes as Carriers: From Drug Delivery to Biosensors

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