Carrier Erythrocytes Research Articles

Erythrocytes as biological carriers and their processing when constructing IHA diagnosticum for detecting melioidosis antibodies in serum

The aim of this study was to increase the efficiency of biocarrier surface binding when constructing erythrocyte diagnosticums, providing for an improvement in indirect hemagglutination test (IHA) sensitivity. In the production of antigenic melioidosis diagnosticum for IHA, sodium alkylsulfate (SDS) was additionally used along with tannin at the stage of processing formalinized sheep erythrocytes. The combined use of these activators contributes to a significant rise of binding capacity of the erythrocyte carrier, which made it possible to increase the sensitivity of the IHA-diagnosticum 2-4-fold. The possibility of obtained preparation use for detection of melioidosis antibodies in sera of both immunized and animals with melioidosis was shown.

Evaluation of Two Osmosis-Based Methods for the Preparation of Drug Delivery Systems Based on Red Blood Cells.

Erythrocytes have been thoroughly investigated as drug delivery systems for a wide range of therapeutic molecules and using different kinds of loading methods, outstanding the osmosis-based methods as the most used ones. Most of them involve too much handling of blood components and the immediate obtention of fresh blood. Based on our group's considerable experience in dialysis-based carrier erythrocyte preparation, this study details a simple method based on hypotonic dilution and subsequent resealing that has been developed for stavudine using packed erythrocytes from a local blood bank. Properties of the obtained carrier erythrocytes were studied in comparison to those prepared by dialysis. Erythrocytes' morphology, osmotic fragility, hematological parameters, and in vitro release profiles were evaluated. Loaded erythrocytes obtained with the proposed method did not show impaired properties in comparison with those obtained with our reference method, provided that the buffer composition remained the same. In the present work, we have optimized a simplified method for erythrocytes' drug loading, which can use blood transfusion products and could be easily automatized and scalable.

A-Synuclein and lipids in erythrocytes of Gaucher disease carriers and patients before and after enzyme replacement therapy.

It is well established that patients with Gaucher disease, as well as carriers of the disease have an increased risk for developing Parkinson's disease. A plethora of evidence suggests that disturbed α-Synuclein homeostasis is the link between Gaucher disease and Parkinson's disease. The pathogenic mechanism linking these entities is still a topic of debate and both gain- and loss-of-function theories have been put forward, which however are not mutually exclusive. In the present study we expanded our previous studies to include not only Gaucher disease patients but also Gaucher disease carriers and Gaucher disease patients following Enzyme Replacement Therapy. In these groups we investigated α-Synuclein in red blood cell membranes in association with lipid abnormalities described in Gaucher disease. These included glucosylceramide and its species, glucosylsphingosine, glucosylcholesterol and plasmalogens. Increased oligomerization of α-Synuclein in red blood cell membranes was observed not only in Gaucher disease patients but also in carriers of the disease. There were no qualitative differences in the lipids identified in the groups studied. However, significant quantitative differences compared to controls were observed in Gaucher disease patients but not in Gaucher disease carriers. Enzyme Replacement Therapy reversed the biochemical defects and normalized α-Synuclein homeostasis, providing for the first time evidence in human subjects that such homeostatic dysregulation is reversible. Further studies investigating α-Synuclein status during the differentiation of erythroid progenitors could provide new data on the pathogenic mechanism of α-Synuclein oligomerization in this system.

A combination of carrier erythrocytes and artificial nanoparticles as a promising approach for drug delivery: a review

A combination of carrier erythrocytes and artificial nanoparticles as a promising approach for drug delivery: a review

A combination of carrier erythrocytes and artificial nanoparticles as a promising approach for drug delivery: a review

A combination of carrier erythrocytes and artificial nanoparticles as a promising approach for drug delivery: a review

Mitochondrial neurogastrointestinal encephalomyopathy in a Pakistani female: a case report

BackgroundMitochondrial neurogastrointestinal encephalopathy is a rare multisystem autosomal recessive disease caused by mutations in the TYMP gene, that encodes for thymidine phosphorylase. Mitochondrial neurogastrointestinal encephalopathy is a progressive degenerative disease characterized by a distinctive tetrad of gastrointestinal dysmotility, peripheral neuropathy, ophthalmoplegia with ptosis, and asymptomatic leukoencephalopathy. It provides a diagnostic dilemma to physicians in regions like Pakistan because of a lack of genetic study availability and associated financial constraints of the population. However, with careful examination and a few basic investigations, mitochondrial neurogastrointestinal encephalopathy can be diagnosed by ruling out most of the close differentials.Case presentationWe report the case of a 23-year-old Asian female whose chief complaints were epigastric pain, bilious emesis, weight loss for 3 months, and bilateral lower limb weakness for 20 days. All clinical signs and symptoms along with relevant investigations including nerve conduction studies, electromyography, and magnetic resonance imaging of the brain were highly suggestive of mitochondrial neurogastrointestinal encephalopathy syndrome. Because of financial constraints, genetic studies could not be performed. The patient was managed with a multidisciplinary approach involving gastroenterology, physiotherapy, and nutrition departments. Currently, therapeutic options for the disease include allogeneic hematopoietic stem cell transplant and carrier erythrocyte entrapped thymidine phosphorylase; however, these could not be provided to the patient owing to certain limitations.ConclusionsAs misdiagnosis and delayed diagnosis are quite common in this disease, the prime objective of this case report is to increase the basic understanding of this disease, especially its signs and symptoms, and address the limitations regarding the diagnostic investigations and management of patients with mitochondrial neurogastrointestinal encephalopathy.

Effect of Silver Nanoparticles Synthesized from Azadirachta indica Leaves Extract on Sickle Erythrocyte Membrane Stability

Aim: To synthesize silver nanoparticles (AgNPs) from Azadirachta indica leaf extract and determine its effect on membrane stability.
 Place and Duration of Study: Department of Biochemistry, Sokoto State University, Sokoto, Nigeria, between January 2021 and April 2021.
 Methodology: Simple characterization using uv-vis spectroscopy was conducted and the well-known method for osmotic fragility was employed.
 Results: Surface plasmon excitation for conversion of Ag+ to AgNPs was successfully achieved at 320 nm. The result revealed increase in membrane stability with 67.50 % for sickle erythrocyte (HbSS), 33.33 % for carrier erythrocyte (HbAS) and 23.33 % for normal erythrocyte (HbAA); thereby decreasing the erythrocyte lysis in the order of HbSS>HbAS>HbAA.
 Conclusion: AgNPs synthesized from A. indica reduces osmotic fragility and hence increases membrane stabilizing potential particularly against sickle erythrocyte.

Novel engineering: Biomimicking erythrocyte as a revolutionary platform for drugs and vaccines delivery

Over the years, extensive studies on erythrocytes, also known as red blood cells (RBCs), as a mechanism for drug delivery, have been explored mainly because the cell itself is the most abundant and has astonishing properties such as a long life span of 100–120 days, low immunogenicity, good biocompatibility, and flexibility. There are various types of RBC-based systems for drug delivery, including those that are genetically engineered, non-genetically engineered RBCs, as well as employing erythrocyte as nanocarriers for drug loading. Although promising, these systems are still in an early development stage. In this review, we aimed to highlight the development of biomimicking RBC-based drug and vaccine delivery systems, as well as the loading methods with illustrative examples. Drug-erythrocyte associations will also be discussed and highlighted in this review.We have highlighted the possibility of exploiting erythrocytes for the sustained delivery of drugs and vaccines, encapsulation of these biological agents within the erythrocyte or coupling to the surface of carrier erythrocytes, and provided insights on genetically- and non-genetically engineered erythrocytes-based strategies.Erythrocytes have been known as effective cellular carriers for therapeutic moieties for several years. Herein, we outline various loading methods that can be used to reap the benefits of these natural carriers. It has been shown that drugs and vaccines can be delivered via erythrocytes but it is important to select appropriate methods for increasing the drug encapsulated or conjugated on the surface of the erythrocyte membrane. The outlined examples will guide the selection of the most effective method as well as the impact of using erythrocytes as delivery systems for drugs and vaccines.

Erythrocyte as an ideal carrier for intavascular drug delivery

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.

Red blood cell-hitchhiking chitosan nanoparticles for prolonged blood circulation time of vitamin K1

Nanocarriers have been extensively applied for intravascular drug delivery. However, rapid clearance from circulation by mononuclear phagocyte system has limited their applications. Erythrocytes carriers are potential solutions to overcome the limitations of nanocarriers and considered to be ideal natural carriers for drug delivery because of their unique properties. The purpose of this work is to combine nanocarriers with erythrocytes carriers for sustained release and prolonged circulation time of vitamin K1. Chitosan nanoparticles loading VK1 (VK-CSNPs) were prepared using ionotropic gelation method, which was optimized using box-behnken design and response surface methodology. VK-CSNPs adsorbed onto red blood cells (RBC-VK-CSNPs) rapidly via electrostatic interactions. The exposure of phosphatidylserine, osmotic fragility and turbulence fragility of RBC loading nanoparticles were investigated to study the toxicity of nanoparticles to erythrocytes. In vivo pharmacokinetic study indicated that Cmax, AUC and MRT of RBC-VK-CSNPs group were remarkably higher than that of VK-CSNPs group. Flow cytometry showed VK-CSNPs steadily retained on the surface of RBC for a long time without affecting the circulation profiles of RBC themselves. The nanoparticles carried on RBC released drug, desorbed and were eliminated in vivo. Therefore, the circulation time of RBC-hitchhiking chitosan nanoparticles was greatly prolonged compared with nanoparticles alone. RBC-hitchhiking could be a valuable hybrid strategy for prolonging the in vivo life of nanocarriers.

Erythrocyte-derived drug delivery systems in cancer therapy

As natural blood components, erythrocytes were good candidates for being used as drug delivery systems to improve the pharmacokinetics, biocompatibility and many other aspects of different drugs. The advantages brought by erythrocytes making erythrocyte-derived drug delivery systems, also known as erythrocyte carriers, suitable for various anti-cancer agents, especially newly invented agents like nanoparticles, which were characterized by their undesired systematic toxicity, anaphylactic reactions and poor biocompatibility. Current researches on erythrocyte carriers in cancer therapy showed inspiring results in four major aspects: cancer enzyme therapy, delivering chemotherapeutic agents, combining with nanoparticles, and several other anti-cancer agents for gene or immune therapy. This novel delivering system was now undergoing the translation process from laboratory to clinical practice. Erythrocyte carriers for cancer enzyme therapy have entered the stage of clinical trial and have showed promising outcomes, and others were still at pre-clinical stage. In summary, erythrocyte-derived drug delivery system might play an indispensable role in the management of cancer in the future.

Erythrocyte as novel cellular drug delivery system

Nowadays so many carrier systems are used for delivery of drug or any other therapeutic agent to specific tissues or cells for achieving desired therapeutic efficacy. Using drug delivery systems can improve action of therapeutic agent and reduce their toxicity. As a novel approach the erythrocyte or red blood cells are used for drug delivery. The resealed erythrocyte is a cellular carrier have more advantage than other carrier system. Based on various studies found that erythrocyte have greater potential in delivery of biopharmaceuticals, therapeutically significant peptides and proteins, nucleic acid-based biological, antigens, anticancer drug and vaccines. The main problem obtain in case of existing carrier systems are biocompatibility of carrier and its degradation products. The biocompatibility, non-pathogenicity, non-immunogenicity and biodegradability make erythrocyte unique and useful carriers. They also possess longer circulation half-life and zero order drug release kinetics. Resealed erythrocyte carriers have certain impact among the activity of certain therapeutic agent like anti-inflammatory drugs, steroids, chemotherapeutic agents by reducing their side effect upon incorporation with these carriers. The general preparation step of resealed erythrocyte involve separation of erythrocyte from blood the organism of interest and using different methods the erythrocyte broken and the therapeutic agent or drug entrapped into the erythrocyte. This review article highlights the characteristics, isolation techniques of erythrocyte, preparation method, evaluation, application of resealed erythrocyte as carrier in drug delivery systems.

Red Blood Cells are Appropriate Carrier for Coagulation Factor VIII.

Aims Factor VIII (FVIII) replacement therapy remains a primary treatment for hemophilia A, however, the development of FVIII antibodies (inhibitors) and short half-life of the FVIII products are the major complications. Erythrocytes may prevent rapid removal of drugs from plasma. Erythrocytes are biocompatible and non-immunogenic drug delivery. In this study, in vitro activity of FVIII encapsulated by human erythrocytes was investigated.Methods FVIII was loaded into erythrocytes using the hypo-osmotic dialysis technique. FVIII activity assay has been analyzed using Activated Partial Thromboplastin Time (APTT). Presence of FVIII on erythrocytes was detected by western blotting and flowcytometry using specific monoclonal antibody (abcam, U.K) against FVIII. Moreover, the osmotic fragility and hematologic parameters of FVIII-loaded carrier erythrocytes were measured.Results Our results indicated that FVIII could not cross the membrane, where plenty of FVIII was found on the surface of the carrier erythrocyte. Flow cytometery results showed that 11% of the loaded carrier erythrocytes was positive for FVIII protein on their surface.The greatest activation of FVIII in both groups including lysate and non-lysate FVIII-loaded RBCs was observed on the first day, and the coagulant activity of this factor was gradually reduced on days 3 and 5. In 1:50 dilution of both groups, significant differences in FVIII activity were observed in 1:50 dilution of both groups, especially on the 5th day.Conclusion This study aims to introduce erythrocytes as appropriate carriers for FVIII to prolong the dosing intervals in the effective and safe levels for a relatively longer time.

Erythrocytes as Carriers of Therapeutic Enzymes.

Therapeutic enzymes are administered for the treatment of a wide variety of diseases. They exert their effects through binding with a high affinity and specificity to disease-causing substrates to catalyze their conversion to a non-noxious product, to induce an advantageous physiological change. However, the metabolic and clinical efficacies of parenterally or intramuscularly administered therapeutic enzymes are very often limited by short circulatory half-lives and hypersensitive and immunogenic reactions. Over the past five decades, the erythrocyte carrier has been extensively studied as a strategy for overcoming these limitations and increasing therapeutic efficacy. This review examines the rationale for the different therapeutic strategies that have been applied to erythrocyte-mediated enzyme therapy. These strategies include their application as circulating bioreactors, targeting the monocyte–macrophage system, the coupling of enzymes to the surface of the erythrocyte and the engineering of CD34+ hematopoietic precursor cells for the expression of therapeutic enzymes. An overview of the diverse biomedical applications for which they have been investigated is also provided, including the detoxification of exogenous chemicals, thrombolytic therapy, enzyme replacement therapy for metabolic diseases and antitumor therapy.

An Advanced Review on Resealed Erythrocytes

Now a days there are numerous applications have been proposed for the use of resealed erythrocytes as carrier for drugs, enzyme replacement therapy etc. Until other carrier systems come of age, resealed erythrocytes technology will remain an active field for the further research. The use of resealed erythrocytes shows potential for a safe and effective delivery of various bioactive molecules for effective targeting. In coming future, erythrocyte based drug delivery system with their capability to afford controlled and site specific drug delivery have been developed for disease management. Erythrocyte carriers are “Nano devices in the field of Nanotechnology”. A large amount of valuable work is needed so as to utilize the potentials of erythrocytes in passive as well as active targeting of drugs in diseases like cancer. At present erythrocytes are most effective carriers in novel drug delivery systems considering their tremendous potential. Hence the present article is reviewed about method of drug loading, evaluation and applications of RSE.

Study of Desorbtion and Exemption of Terpeno-indole Alkaloids of Vinkristin and Vinblastin from Erythrocitary Cell Carriers

Introduction. Employees of the Department of Pharmaceutical Chemistry and Pharmaceutical Technology have obtained modified forms of terpino-indole alkaloids (ТIA) and vinbristine (VCR) and vinblastine (VBL) known in the treatment of cancer diseases by incorporating them into the erythrocyte carriers (EN) by the modified method of hypoosmotic lysis in the modified (aprotic solvent dimethyl sulfoxide (DMSO) and polyethylene glycol (PEG 4000) and unmodified media.Aim. The aim of the work was to study the desorption and release of terpene-indole vincristine and vinblastine alkaloids from previously obtained cellular erythrocyte carriers.Materials and methods. In the experiment performed, the release characteristics of encapsulated preparations from erythrocytes were determined. TIA preparations were released from erythrocyte form in 6 hours: VCR – 54.5305%, VCR : PEG-4000 (1:5) – 53.3305%, VCR : PEG-4000 (1:10) – 40.1283%, VCR : PEG-4000 (1:20) – 39.9869%, VCR : DMSO (2 mg/ml) – 54.2354%, VBL – 68.0656%; VBL : PEG-4000 (1:10) – 63.8941%; VBL : PEG-4000 (1:20) – 60.7455%; VBL : PEG-400 (1:20) – 60.3529%; VBL : DMSO (2 mg/ml) – 64.5006%. The rate of release from an erythrocyte form encapsulated in a medium modified with DMSO is significantly higher than that encapsulated in an unmodified medium. The average rate of TIA release from erythrocyte forms encapsulated in PEG medium is approximately the same.Results and discussion. The results show that the release of hemoglobin from TIA encapsulated erythrocytes compared with non-encapsulated EN is small. The results show that, on average, 8.242 ± 0.3135% of hemoglobin is released from TIA encapsulated with EN, compared to control erythrocytes – 7.53% after 6 h of incubation at 37 °C. The release of hemoglobin from the TIA of encapsulated erythrocytes in modified media is less than that encapsulated in unmodified medium.Conclusion. Based on these results, it can be suggested that PEG can bind to the erythrocyte membrane and stabilize it.

Design and evaluation of anti-fibrosis drug engineered resealed erythrocytes for targeted delivery.

Resealed erythrocytes (RSE) are potential, site-specific carrier system for drug delivery with prolonged drug release activity. In this study, erythrocytes obtained from Wistar albino rats were loaded with ambroxol hydrochloride (AH) with the focus to convenience the lung targeting possibility of the carrier erythrocytes. AH loading in erythrocytes using preswell dilution technique with glutaraldehyde (GA) as a cross-linking agent was evaluated and validated. Drug-loaded erythrocyte was characterized in terms of in vitro drug release followed by osmotic fragility study which showed amplified drug entrapment efficiency (DEE) and hemoglobin content values as well. In vivo lung fibrosis study, rats were sensitized to egg albumin by intraperitoneal (i.p.) injection and then inhalation in a whole body inhalation chamber. A sign of inflammation, airway sub-mucosal fibrosis, hypertrophy, and hyperplasia was observed. A series of in vivo studies were carried out to describe the effect of AH-loaded RSE including measurement of cytokines in Bronchoalveolar Lavage (BAL) fluid and histopathology study. AH showed a stepwise reduced level of cytokines in BAL at a different time interval after being injected of AH-loaded RSE. Furthermore, in vivo lung distribution experiments were performed for optimized formulation, and degree of distribution of the drugs inside the targeted organ was found to be satisfactory.

Resealed RBC's: Method, Evaluation, Route of Administration and Application

Blood sample from the organism of interest and separating among the various carriers used for targeting drugs to various body tissues, the cellular carriers meet several criteria among the foremost necessary being biocompatibility of carrier and its degradation merchandise. Leucocytes, platelets, erythrocytes, nanoerythrocytes, hepatocytes, and fibroblasts etc. have been proposed as cellular carrier systems. Among these, the erythrocytes have been the most investigated and have found to possess greater potential in drug delivery. Erythrocytes, conjointly referred to as red blood cells, and are extensively studied for his or her potential carrier capabilities for the delivery of medicine. The biocompatibility, nonpathogenicity, non-immunogenicity and biodegradability create them distinctive and helpful carriers. Carrier erythrocytes are prepared by collecting erythrocytes from plasma. By using varied ways that, the cells square measure broken and therefore the drug is entrapped into the erythrocytes, finally (they square measure and therefore the resultant carriers are then known as resealed So many medications like salicylate, steroid, cancer drug which having many side effects are reduce by erythrocyte. Current review highlights isolation, drug loading ways, analysis ways and applications of erythrocytes.

Important Role, Isolation and Basic Concept of Resealed Erythrocytes

Among the most important being biocompatibility of carrier and its degradation products erythrocytes the most investigated and have found to possess greater potential in drug delivery Erythrocytes, also known as red blood cells, and have been extensively studied for their potential carrier capabilities for the delivery of drugs. The biocompatibility, non-pathogenicity, non-immunogenicity and biodegradability make them unique and useful carriers. Carrier erythrocytes are prepared by collecting blood sample from the organism of interest and separating erythrocytes from plasma. The concept of employing erythrocytes as drug or bio active carrier still needs further optimization a large amount of valuable work is needed so us to utilize the potential of erythrocyte in passive and as well as active targeting of drugs. Disease like cancer would surely find it cure. Genetic engineering aspects can be coupled to give a newer dimension to the existing cellular drug concept.

Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE-MTDPS1).

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE-MTDPS1) is a devastating autosomal recessive disorder due to mutations in TYMP, which cause a loss of function of thymidine phosphorylase (TP), nucleoside accumulation in plasma and tissues, and mitochondrial dysfunction. The clinical picture includes progressive gastrointestinal dysmotility, cachexia, ptosis and ophthalmoparesis, peripheral neuropathy, and diffuse leukoencephalopathy, which usually lead to death in early adulthood. Other two MNGIE-type phenotypes have been described so far, which are linked to mutations in POLG and RRM2B genes. Therapeutic options are currently available in clinical practice (allogeneic hematopoietic stem cell transplantation and carrier erythrocyte entrapped thymidine phosphorylase therapy) and newer, promising therapies are expected in the near future. Since successful treatment is strictly related to early diagnosis, it is essential that clinicians be warned about the clinical features and diagnostic procedures useful to suspect diagnosis of MNGIE-MTDPS1. The aim of this review is to promote the knowledge of the disease as well as the involved mechanisms and the diagnostic processes in order to reach an early diagnosis.