Erythrocytes as Carriers for L-Asparaginase. Methodological and Mouse In-vivo Studies

Kravtzoff, Roger; Ropars, C.; Laguerre, M.; Müh, J.P.; Chassaigne, M

doi:10.1111/j.2042-7158.1990.tb06598.x

Cited by 66 publications

(46 citation statements)

References 12 publications

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“…Thus to increase the outcome of the treatment, improving both pharmacokinetic parameters and enzyme efficacy, L-asparaginase loaded-erythrocytes have been proposed. Asparaginase has been first encapsulated in vitro into RBC revealing that Asn rapidly entered the red cells and was metabolized by the loaded enzyme in situ (63,86,87). This was confirmed in several animal models (63,(64)(65)(66)(67).…”

Section: Red Blood Cells As Enzyme Carriersmentioning

confidence: 72%

“…Asparaginase has been first encapsulated in vitro into RBC revealing that Asn rapidly entered the red cells and was metabolized by the loaded enzyme in situ (63,86,87). This was confirmed in several animal models (63,(64)(65)(66)(67). These findings led to the clinical exploitation of asparaginase-loaded RBC through human clinical trials in which both pharmacody- Figure 5.…”

Section: Red Blood Cells As Enzyme Carriersmentioning

confidence: 72%

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Drug delivery by red blood cells

et al. 2011

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SummaryDrug delivery is a growing field of interdisciplinary activities that combine the use of new materials with the biochemical properties of selected drugs, with the aim of improving their therapeutic action and reducing their toxicity. In few cases, proper medical devices have been also realized to implement new drug delivery modalities. In this article, we have summarized available information and our experience on the use of autologous Red Blood Cells as carriers for drugs to be released within the vascular system. This is not a comprehensive review, but it focusses on the mechanisms that are available to distribute drugs in circulation by carrier red blood cells and provide illustrative examples on how this is currently obtained. We have not included a summary of clinical data collected in recent years using this technology but simply provided proper references for the interested readers. Finally, a special attention is devoted to the possibility of entrapping, into autologous red blood cells, recombinant drug-binding proteins. This new strategy is opening the way at a new modality to influence the vascular distribution of drugs by realizing a dynamic circulating container (the engineered red cell) capable of reversible binding and transportation of one or more drugs of interest selected on the bases of the red cell entrapped target proteins. This new modality is not yet fully developed and explored but will certainly provide a technical solution to the problem of stabilizing drug concentration in circulation improving drug efficacy and reducing drug toxicity.

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Section: Red Blood Cells As Enzyme Carriersmentioning

confidence: 72%

Section: Red Blood Cells As Enzyme Carriersmentioning

confidence: 72%

Drug delivery by red blood cells

et al. 2011

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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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“…They include entrapment into liposomes [10] or erythrocytes [11], and conjugation to mPEG [12]. In our recent work with polysialylation, activated colominic acid (see legend to fig.…”

Section: Polysialylated Asparaginasementioning

confidence: 99%

Polysialic acids: potential in improving the stability and pharmacokinetics of proteins and other therapeutics

Gregoriadis¹,

Fernandes²,

Mital³

et al. 2000

CMLS, Cell. Mol. Life Sci.

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Naturally occurring polymers of N-acetylneuraminic acid (polysialic acids) are biodegradable, highly hydrophilic and have no known receptors in the body. Following intravenous injection, polysialic acids exhibit long half-lives in the blood circulation and have therefore been proposed as carriers of short-lived drugs and small peptides. In addition, shorter-chain polysialic acids can be used as a means to increase the circulatory half-life of proteins and thus serve as an alternative to the nonbiodegradable monomethoxypoly(ethylene glycol). Recent work has shown that covalent coupling of a low molecular weight polysialic acid (colominic acid) to catalase and asparaginase leads to a considerable increase of enzyme stability in the presence of proteolytic enzymes or blood plasma. Comparative studies in vivo with polysialylated and intact asparaginase revealed that polysialylation significantly increases the half-life of the enzyme. The highly hydrophilic and innocuous nature of polysialic acids renders them suitable as a means to prolong the circulation of peptides and proteins.

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Erythrocytes as Carriers for L-Asparaginase. Methodological and Mouse In-vivo Studies

Cited by 66 publications

References 12 publications

Drug delivery by red blood cells

Drug delivery by red blood cells

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

Polysialic acids: potential in improving the stability and pharmacokinetics of proteins and other therapeutics

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