Rapid Elimination of Blood Alcohol Using Erythrocytes: Mathematical Modeling and In Vitro Study

Alexandrovich, Yuliya G.; Kosenko, Elena; Sinauridze, Elena I.; Obydennyi, Sergey I.; Kireev, Igor I.; Ataullakhanov, F. I.; Kaminsky, Yuriy G.

doi:10.1155/2017/5849593

Cited by 12 publications

(15 citation statements)

References 38 publications

(50 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several years later Lizano et al [74,75] in attempts to increase alcohol consumption by enzyme-loaded erythrocytes, co-encapsulated both alcohol dehydrogenase and acetaldehyde dehydrogenase from yeast without a significant improvement in alcohol degradation with respect to the figures found using a single enzyme. Furthermore, Alexandrovich et al [76], using in vitro studies and mathematical modeling, concluded that the metabolic ability of enzyme-loaded erythrocytes to degrade ethanol is not limited by the amount of enzyme(s) loaded but rather by the NAD + / NADH ratio inside the cell, confirming a previous observation [2]. It is noteworthy that several experiments were performed using a low-affinity acetaldehyde dehydrogenase rather than a high-affinity enzyme for acetaldehyde.…”

Section: Alcohol Detoxificationsupporting

confidence: 55%

Preclinical developments of enzyme-loaded red blood cells

Rossi

Pierigé

Bregalda

et al. 2020

Expert Opinion on Drug Delivery

View full text Add to dashboard Cite

Introduction: Therapeutic enzymes are currently used in the treatment of several diseases. In most cases, the benefits are limited due to poor in vivo stability, immunogenicity, and drug-induced inactivating antibodies. A partial solution to the problem is obtained by masking the therapeutic protein by chemical modifications. Unfortunately, this is not a satisfactory solution because frequent adverse events, including anaphylaxis, can arise. Area covered: Among the delivery systems, we focused on red blood cells for the delivery of therapeutic enzymes. Erythrocytes possess a long circulation time, a reduced immunogenicity, there is no need of chemical modifications and the encapsulated enzyme remains active because it is protected by the cell membrane. Here we discuss some representative applications of the preclinical developments of the field. Some of these are currently in clinic, others are approaching the clinic and others are illustrative of the development process. The selected examples are not always the most recent, but they are the most useful for a comparative approach. Expert opinion: The results discussed confirm the central role that red blood cells can play in the treatment of several conditions and suggest the benefit in using a natural cellular carrier in terms of pharmacokinetic, biodistribution, safety, and efficacy.

show abstract

Section: Alcohol Detoxificationsupporting

confidence: 55%

Preclinical developments of enzyme-loaded red blood cells

Rossi

Pierigé

Bregalda

et al. 2020

Expert Opinion on Drug Delivery

View full text Add to dashboard Cite

show abstract

“…EBRs for removal of low molecular metabolites (ethanol, methanol, cyanide, glucose or ammonium) from bloodstream have been described. These EBRs were based on alcohol dehydrogenase [11,59,60], alcohol oxidase [61], acetaldehyde dehydrogenase [11,62] or alcohol-and acetaldehyde dehydrogenase together [63] in cases of ethanol, methanol and acetaldehyde removal.…”

Section: Erythrocytes-bioreactors For Low Molecular Metabolites Utilimentioning

confidence: 99%

“…β-Galactosidase - [21] β-Glucocerebrosidase (β-glucosidase) Gaucher disease [21,37,38,[44][45][46]250] β-Glucuronidase Syndrome Slaya [251] l-Phenylalanine ammonia lyase Phenylketonuria [48,252,253] Phenylalanine hydroxylase [50,254] Uricase (uratoxidase) Uric acid removal [255,256] Urease, urease + alanine dehydrogenase Urea utilization [257][258][259] Adenosine deaminase Severe combined immunodeficiency caused by deaminase deficiency [27,[55][56][57][58]260] Thymidine phosphorylase Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) [56,246,261,262] Glutamate dehydrogenase Hyperammonemia [59,60,72] Glutamine synthetase [73,74] Glutamate dehydrogenase + alanine aminotransferase [11,63] Arginase Hyperammonemia due to arginase deficiency [263] Alcohol dehydrogenase…”

Section: Active Substance Application Referencesmentioning

confidence: 99%

See 1 more Smart Citation

Erythrocytes as Carriers: From Drug Delivery to Biosensors

et al. 2020

View full text Add to dashboard Cite

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...

show abstract

“…This is a limitation for the use of the wider class of active compounds that are unable to be transported into the cells. We tried to circumvent this problem and developed a technology of the encapsulation of substrates and high molecular enzymes in erythrocytes under hypotonic conditions leading to the formation of pores in the membranes of erythrocytes (Seeman et al, 1973 ), enabling the enzymes with great molecular mass (Baker, 1967 ; Kosenko et al, 2008b ; Godfrin et al, 2012 ; Kaminsky and Kosenko, 2012 ; Alexandrovich et al, 2017 ) to pass through the cells. For instance, we developed an approach on how to introduce regulatory glycolytic enzymes into erythrocytes, where the activity of these enzymes in erythrocytes of old animals and in the elderly decreased by 30–50% (Kaminsky et al, 2013 ).…”

Section: Novel Therapeutic Strategy: Problems and Possible Solutionsmentioning

confidence: 99%

Metabolic Abnormalities of Erythrocytes as a Risk Factor for Alzheimer's Disease

et al. 2018

Self Cite

View full text Add to dashboard Cite

Alzheimer's disease (AD) is a slowly progressive, neurodegenerative disorder of uncertain etiology. According to the amyloid cascade hypothesis, accumulation of non-soluble amyloid β peptides (Aβ) in the Central Nervous System (CNS) is the primary cause initiating a pathogenic cascade leading to the complex multilayered pathology and clinical manifestation of the disease. It is, therefore, not surprising that the search for mechanisms underlying cognitive changes observed in AD has focused exclusively on the brain and Aβ-inducing synaptic and dendritic loss, oxidative stress, and neuronal death. However, since Aβ depositions were found in normal non-demented elderly people and in many other pathological conditions, the amyloid cascade hypothesis was modified to claim that intraneuronal accumulation of soluble Aβ oligomers, rather than monomer or insoluble amyloid fibrils, is the first step of a fatal cascade in AD. Since a characteristic reduction of cerebral perfusion and energy metabolism occurs in patients with AD it is suggested that capillary distortions commonly found in AD brain elicit hemodynamic changes that alter the delivery and transport of essential nutrients, particularly glucose and oxygen to neuronal and glial cells. Another important factor in tissue oxygenation is the ability of erythrocytes (red blood cells, RBC) to transport and deliver oxygen to tissues, which are first of all dependent on the RBC antioxidant and energy metabolism, which finally regulates the oxygen affinity of hemoglobin. In the present review, we consider the possibility that metabolic and antioxidant defense alterations in the circulating erythrocyte population can influence oxygen delivery to the brain, and that these changes might be a primary mechanism triggering the glucose metabolism disturbance resulting in neurobiological changes observed in the AD brain, possibly related to impaired cognitive function. We also discuss the possibility of using erythrocyte biochemical aberrations as potential tools that will help identify a risk factor for AD.

show abstract

Rapid Elimination of Blood Alcohol Using Erythrocytes: Mathematical Modeling and In Vitro Study

Cited by 12 publications

References 38 publications

Preclinical developments of enzyme-loaded red blood cells

Preclinical developments of enzyme-loaded red blood cells

Erythrocytes as Carriers: From Drug Delivery to Biosensors

Metabolic Abnormalities of Erythrocytes as a Risk Factor for Alzheimer's Disease

Contact Info

Product

Resources

About