Pharmacokinetics of Doxorubicin in Patients with Lymphoproliferative Disorders after Infusion of Doxorubicin-Loaded Erythrocytes

Ataullakhanov, Fazoil I.; Isaev, V G; Kohno, Alina V.; Куликова, Е. В.; Паровичникова, Е Н; Savchenko, Valery G.; Vitvitsky, Victor

doi:10.1007/978-1-4899-0044-9_18

Cited by 6 publications

(8 citation statements)

References 13 publications

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“…For the free form of doxorubicin, the concentration of the drug rapidly decreased within 10-30 min after administration, and after 12-24 h the concentration decreased to zero. A similar picture was observed for doxorubicin in erythrocytes in the fast phase, but after the plasma doxorubicin concentration decreased to 0.1 µg/mL, its level remained almost constant up to 3 days [109]. In a recent paper [111], the cardiotoxicity of doxorubicin in carrier erythrocytes obtained by electroporation was studied in healthy mice.…”

Section: Anthracycline Antibioticssupporting

confidence: 57%

“…Pilot studies of RBCs loaded with anthracycline antibiotics in patients with leukemia and lymphomas were carried out by a group of Russian authors (Ataullakhanov et al). They demonstrated the advantages of the administration of daunorubicin-and doxorubicin-loaded RBCs compared with the administration of the free medicines [107][108][109][110]. Both drugs in the RBCs were clinically effective and were better tolerated by patients.…”

Section: Anthracycline Antibioticsmentioning

confidence: 99%

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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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Section: Anthracycline Antibioticssupporting

confidence: 57%

Section: Anthracycline Antibioticsmentioning

confidence: 99%

Erythrocytes as Carriers: From Drug Delivery to Biosensors

et al. 2020

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“…7,8 The drug concentration dropped rapidly during the first 10-30 min after the infusion decreasing by one or two orders of magnitude. It then declined slowly to the lower limit of its quantitation.…”

Section: C=cb+a1exp(-t/t1)+a2exp(-t/t2)mentioning

confidence: 99%

“…Statistical analysis included data, obtained earlier in three patients treated with DLE. 7 The experimental protocol was approved by the Scientific Council of the National Research Center for Hematology. Methods and risks were explained and written consent was obtained from each patient.…”

Section: 4mentioning

confidence: 99%

Doxorubicin pharmacokinetics in lymphoma patients treated with doxorubicin-loaded eythrocytes

Skorokhod¹,

Куликова²,

Галкина³

et al. 2007

Haematologica

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Doxorubicin pharmacokinetics in lymphoma patients treated with doxorubicin-loaded eythrocytesDoxorubicin-loaded erythrocytes (DLE) were administrated to 15 lymphoma patients. Antibiotic peak concentration in blood decreased by 55%, doxorubicin circulated several times longer, and the area under the concentration-time curve increased 5 times if compared with standard doxorubicin administration. The DLE was well tolerated by patients.

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“…Скороход и др.) продемонстрировала преимущество введения даунорубицина и доксорубицина в эритроциты по сравнению с введением свободной формы этих препаратов у пациентов с лейкозами и лимфомами [27,28,31]. Препараты в эритроцитах лучше переносились пациентами.…”

Section: пролонгированное действие и снижение побочных эффектов препаunclassified

Erythrocyte as an ideal carrier for intavascular drug delivery

Колева

Ataullakhanov

Sinauridze

2020

Voprosy gematologii/onkologii i immunopatologii v pediatrii

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Drug delivery using natural biological carriers, especially erythrocytes, is a rapidly developing field. Erythrocytes can act as carriers with the gradual release of a pharmacological agent, as bioreactors with encapsulated enzymes, or as a tool for targeted delivery of drugs to target organs especially tissue macrophages, liver and spleen. To date, red blood cells have been studied as carriers for a wide range of drug compounds, such as enzymes, antibiotics, anti-inflammatory, antiviral drugs, etc. The review is devoted to the advantages of erythrocytes as carriers for the delivery of drugs loaded into the erythrocyte, or related to its surface, and defines the main directions of research on erythrocytes carriers of biologically active substances. Particular attention is paid to in vivo studies that reveal the potential of carrier erythrocytes for clinical use.

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Pharmacokinetics of Doxorubicin in Patients with Lymphoproliferative Disorders after Infusion of Doxorubicin-Loaded Erythrocytes

Cited by 6 publications

References 13 publications

Erythrocytes as Carriers: From Drug Delivery to Biosensors

Erythrocytes as Carriers: From Drug Delivery to Biosensors

Doxorubicin pharmacokinetics in lymphoma patients treated with doxorubicin-loaded eythrocytes

Erythrocyte as an ideal carrier for intavascular drug delivery

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