Nanocarriers' repartitioning of drugs between blood subcompartments as a mechanism of improving pharmacokinetics, safety, and efficacy.

For medical emergencies, such as acute ischemic stroke, rapid drug delivery to the target site is essential. For many small molecule drugs, this goal is unachievable due to poor solubility that prevents intravenous administration, and less obviously, by extensive partitioning to plasma proteins and red blood cells (RBCs), which greatly slows delivery to the target. Here we study these effects and how they can be solved by loading into nanoscale drug carriers. We focus on fingolimod, a small molecule drug that is FDA-approved for treatment of multiple sclerosis, which has also shown promise in the treatment of stroke. Unfortunately, fingolimod has poor solubility and very extensive partitioning to plasma proteins and RBCs (in whole blood, 86% partitions to RBCs, 13.96% to plasma proteins, and 0.04% is free). We develop a liposomal formulation that slows the partitioning of fingolimod to RBCs and plasma proteins, enables intravenous delivery, and additionally prevents fingolimod toxicity to RBCs. The liposomal formulation nearly completely prevented fingolimod adsorption to plasma proteins (association with plasma proteins was 98.4 ±â€¯0.4% for the free drug vs. 5.6 ±â€¯0.4% for liposome-loaded drug). When incubated with whole blood in vitro, the liposomal formulation greatly slowed partitioning of fingolimod to RBCs and also eliminated deleterious effects of fingolimod on RBC rigidity, morphology, and hemolysis. In vivo, the liposomal formulation delayed fingolimod partitioning to RBCs for over 30 min, a critical time window for stroke. Fingolimod-loaded liposomes showed improved efficacy in a mouse model of post-stroke neuroinflammation, completely sealing the leaky blood-brain barrier (114 ±â€¯11.5% reduction in albumin leak into the brain for targeted liposomes vs. 38 ±â€¯16.5% reduction for free drug). This effect was only seen for liposomes modified with antibodies to enable targeted delivery to the site of action, and not in unmodified, long-circulating liposomes. Thus, loading fingolimod into liposomes prevented partitioning to RBCs and associated toxicities and enabled targeted delivery. This paradigm can be used for tuning the blood distribution of small molecule drugs for the treatment of acute illnesses requiring rapid pharmacologic intervention.

Anion exchanger1 (AE1/SLC4A1) function is impaired in red blood cells from prediabetic subjects: Potential benefits of finger lime (Citrus australasica, Faustrime cultivar) juice extract.

Prediabetes is a risk state that defines a high chance of developing diabetes and cardiovascular disease. Oxidative stress mediated by hyperglycemia-induced production of reactive species could play a crucial role in this context. In the present study, we investigated whether the anion exchange capability mediated by AE1 (SLC4A1), which is sensitive to oxidative stress, was altered in human red blood cells (RBCs) obtained from prediabetic volunteers. In addition, we assessed the precise composition of bioactive compounds and the potential benefits of finger lime juice extract (Citrus australasica, Faustrime cultivar) in counteracting oxidative stress-related functional alterations. Human RBCs from normal and prediabetic volunteers were incubated with 50 µg/mL juice extract for 2 h at 25°C. Juice extract restored alterations of the anion exchange capability mediated by AE1 and prevented the structural rearrangements of AE1 and α/ß-spectrin in prediabetic RBCs. AE1 functional and structural alterations were not associated with an increase in lipid peroxidation or protein oxidation at the level of the plasma membrane. An increased production of intracellular ROS, which provoked the oxidation of hemoglobin to methemoglobin, both reverted by juice extract, was instead observed. Importantly, juice extract also induced a reduction in glycated hemoglobin levels in prediabetic RBCs. Finally, juice extract blunted the overactivation of the endogenous antioxidant enzymes catalase and superoxide dismutase and prevented glutathione depletion in prediabetic RBCs. These findings contribute to clarifying cellular and molecular mechanisms related to oxidative stress and glycation events that may influence RBC and systemic homeostasis in prediabetes, identify AE1 as a sensitive biomarker of RBC structural and function alterations in prediabetes and propose finger lime juice extract as a natural antioxidant for the treatment and/or prevention of the complications associated with the prediabetic condition.

Understanding the physiological transmission mechanisms of photoplethysmography signals: a comprehensive review.

The widespread adoption of Photoplethysmography (PPG) as a non-invasive method for detecting blood volume variations and deriving vital physiological parameters reflecting health status has surged, primarily due to its accessibility, cost-effectiveness, and non-intrusive nature. This has led to extensive research around this technique in both daily life and clinical applications. Interestingly, despite the existence of contradictory explanations of the underlying mechanism of PPG signals across various applications, a systematic investigation into this crucial matter has not been conducted thus far. This gap in understanding hinders the full exploitation of PPG technology and undermines its accuracy and reliability in numerous applications. Building upon a comprehensive review of the fundamental principles and technological advancements in PPG, this paper initially attributes the origin of PPG signals to a combination of physical and physiological transmission processes. Furthermore, three distinct models outlining the concerned physiological transmission processes are synthesized, with each model undergoing critical examination based on theoretical underpinnings, empirical evidence, and constraints. The ultimate objective is to form a fundamental framework for a better understanding of physiological transmission processes in PPG signal generation and to facilitate the development of more reliable technologies for detecting physiological signals. .

Acute Pain Transfusion Reaction: A Case Report.

Transfusion-related adverse events involving packed red blood cells (PRBCs) and fresh frozen plasma (FFP) are not unusual. Reactions can happen at any time during the transfusion, as well as hours or days later. An acute pain transfusion reaction (APTR) is defined as sudden, intense joint pain, usually in the back and trunk, that appears right after transfusion after all other potential causes of transfusion reactions have been eliminated. The present article discusses two similar cases. A 38-year-old female presented with complaints of right-sided headache and photophobia for four days, associated with nausea, vomiting, and vertigo. She was evaluated for a migraine headache. Due to anemia, a one-unit PRBC was requested. After pre-transfusion testing, a one-unit non-leuko-reduced, coombs cross-match compatible B-positive packed red blood cell (PRBC) was issued and transfused. During the transfusion, the patient complained of chest pain. The transfusion was stopped. Her vitals did not vary much from the baseline. No other symptoms were present at that time. A 69-year-old female presented with complaints of vomiting, abdominal pain, and black tarry stool for a one-month duration. On evaluation, she was diagnosed with adenocarcinoma of the stomach. Given the increased prothrombin time/international normalized ratio (PT/INR) of 1.8, four-units of fresh frozen plasma (FFP) was requested, which was issued after performing minor cross-match compatibility. After five minutes of transfusion, she complained of severe pain at the transfusion site with chills and rigors. The transfusion was stopped. There was no change in the vitals of the patient from baseline. A complete workup was done to rule out other transfusion reactions in both cases. Thus, these patients experienced what is known as an acute pain transfusion reaction. APTR is typically self-limited and requires treatment of symptoms with pain control, supplemental oxygen, and emotional support. In both cases, supportive treatments were enough to control the pain symptoms of the patients.

In vitro Evaluation of DINCH-Plasticized Blood Bags for Red Blood Cell Storage with CPDA-1 Anticoagulant.

Introduction: Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer commonly used in blood bags. Despite its protective effects on red blood cell (RBC) storage, concerns about its reproductive toxicity exist. This study investigated the in vitro quality of RBC concentrates stored in bags using di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) as an alternative plasticizer. Methods: Using a pool-and-split study design, we produced 20 matched homogenous quintets of RBC concentrates in two DINCH bags and three DEHP bags with citrate phosphate dextrose adenine (CPDA-1) anticoagulant. RBC storage quality was assessed weekly for 35 days. Results: On day 35, the median hemolysis levels in the DINCH bags (0.297-0.342%) were marginally higher (p < 0.05) than the DEHP bags (0.204-0.240%). All DINCH bags showed <0.8% hemolysis. RBCs in the DINCH bags showed increased mean corpuscular volume and decreased eosin 5' maleimide binding than in the DEHP bags. Higher pO2 and lower pCO2 levels in the DINCH bags indicated better gas permeability than in DEHP bags. Other metabolic parameters were comparable in both bags. Compared to DEHP, DINCH exhibited considerably lower levels of plasticizer leaching into blood bags. Conclusion: The quality of RBC concentrates stored for 35 days in DINCH-plasticized blood bags with CDPA-1 is generally comparable to those in DEHP bags. Hence, DINCH can be a viable alternative to DEHP in blood bags for nonleukoreduced RBC storage even without the use of next-generation additive solutions to improve RBC preservation quality.

A plasticizer is a chemical substance added to plastic to increase its flexibility. DEHP is a plasticizer that has been widely used in many products including plastic tubing and bags of medical devices. However, concerns about DEHP-related toxicity have been debated for many years. DEHP has been replaced with other plasticizers in many products, but it is still being used in blood bags due to its protective effect on RBC preservation. DINCH is an alternative plasticizer with a low toxicology profile. This study investigated the quality of RBC concentrates stored in blood bags using DINCH. Twenty sets of five RBC concentrates were produced using two DINCH bags and three DEHP bags with CPDA-1 anticoagulant, and the storage quality was assessed weekly for 35 days. On day 35, the median hemolysis levels in the DINCH bags (0.297­0.342%) were slightly increased than the DEHP bags (0.204­0.240%). However, all DINCH bags showed hemolysis lower than the regulatory limit of 0.8%. DINCH bags exhibited better gas permeability than DEHP bags. Compared to DEHP, DINCH exhibited considerably lower levels of plasticizer leaching into blood bags. Most of the other metabolic parameters were comparable in both bags. The quality of nonleukocyte-reduced RBC concentrates stored for 35 days in DINCH-plasticized blood bags with CDPA-1 is generally comparable to those in DEHP bags. Hence, DINCH can be a viable alternative to DEHP in blood bags for RBC storage, even without the use of next-generation additive solutions to improve RBC preservation quality.

51Cr Red Blood Cells in the Study of Hematologic Disease: A Historical Review.

The early years of nuclear medicine included the development and clinical use of several in vitro or nonimaging procedures. The use of radionuclides as replacements for nonradioactive dyes brought improved accuracies and less subjective measurements to indicator dilution studies of body compartments such as the gastrointestinal system, lungs, urinary system, and vascular space. A popular nuclear medicine procedure was the radionuclide dilution method for quantitation of whole-blood volume or red blood cell volume or mass using 51Cr-labeled red blood cells-an important diagnostic element in patients suspected of having polycythemia vera, congestive heart failure, hypertension, shock, syncope, and other abnormal blood volume disorders. The radionuclide dilution method led to improved evaluation of red blood cell survival, which is important for clinical treatment planning in anemia and confirmation of splenic sequestration of damaged red blood cells. Although it was discovered that 51Cr was a chemically stable radiolabel of red blood cells after binding to intracellular hemoglobin, few nuclear medicine departments offered the clinical study for referring physicians because it required laboratory expertise for technologists, patient coordination, and a time-consuming procedure. The introduction of improved methods that are less time-consuming and have clinically acceptable results, along with the discontinuation of the sodium chromate 51Cr injection radiopharmaceutical by manufacturers, has consigned 51Cr red blood cells for red blood cell volume, mass, or survival evaluation to the list of retired nuclear medicine studies.

Multimodal analysis of dysregulated heme metabolism, hypoxic signaling, and stress erythropoiesis in Down syndrome.

Down syndrome (DS), the genetic condition caused by trisomy 21 (T21), is characterized by delayed neurodevelopment, accelerated aging, and increased risk of many co-occurring conditions. Hypoxemia and dysregulated hematopoiesis have been documented in DS, but the underlying mechanisms and clinical consequences remain ill defined. We report an integrative multi-omic analysis of ∼400 research participants showing that people with DS display transcriptomic signatures indicative of elevated heme metabolism and increased hypoxic signaling across the lifespan, along with chronic overproduction of erythropoietin, elevated biomarkers of tissue-specific hypoxia, and hallmarks of stress erythropoiesis. Elevated heme metabolism, transcriptional signatures of hypoxia, and stress erythropoiesis are conserved in a mouse model of DS and associated with overexpression of select triplicated genes. These alterations are independent of the hyperactive interferon signaling characteristic of DS. These results reveal lifelong dysregulation of key oxygen-related processes that could contribute to the developmental and clinical hallmarks of DS.

Could oxygen gradient ektacytometry help to detect sickle cell trait carriers at risk for kidney disorders or exercise-related complications?

The study of Ellsworth et al. (Br J Haematol, 2024) demonstrated the usefulness of oxygen gradient ektacytometry technique to better identify the physiological parameters that could increase the risk of sickling of red blood cells (RBCs) from sickle cell trait (SCT) carriers. Oxygen gradient ektacytometry combined with pH and osmolality modulations could help in identifying SCT carriers at risk for kidney disorders or exercise-related complications. Other factors than the percentages of haemoglobin S are probably involved in the propensity of RBCs from SCT carriers to sickle during deoxygenation. Commentary on: Ellsworth et al. Hypertonicity and/or acidosis induce marked rheological changes under hypoxic conditions in sickle trait red blood cells. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19669.

Corrigendum: Drug transport by red blood cells.

[This corrects the article DOI: 10.3389/fphys.2023.1308632.].

Effects of red blood cell transfusion on patients undergoing cardiac surgery in Queensland - a retrospective cohort study.

BACKGROUND: Packed red blood cell (pRBC) transfusion is a relatively safe and mainstay treatment commonly used in cardiac surgical patients. However, there is limited evidence on clinical effects of transfusing blood nearing end-of shelf life that has undergone biochemical changes during storage. OBJECTIVE: To investigate evidence of associations between morbidity/mortality and transfusion of blood near end of shelf-life (> 35 days) in cardiac surgical patients. METHODS: Data from the Queensland Health Admitted Patient Data Collection database 2007-2013 was retrospectively analysed. Coronary artery bypass graft and valvular repair patients were included. Multivariable logistic regression was used to examine the effect of pRBC age (< 35 days vs. ≥ 35 days) on in-hospital mortality and morbidity. As secondary analysis, outcomes associated with the number of pRBC units transfused (≤ 4 units vs. ≥ 5 units) were also assessed. RESULTS: A total of 4514 cardiac surgery patients received pRBC transfusion. Of these, 292 (6.5%) received pRBCs ≥ 35 days. No difference in in-hospital mortality or frequency of complications was observed. Transfusion of ≥ 5 units of pRBCs compared to the ≤ 4 units was associated with higher rates of in-hospital mortality (5.6% vs. 1.3%), acute renal failure (17.6% vs. 8%), infection (10% vs. 3.4%), and acute myocardial infarction (9.2% vs. 4.3%). Infection carried an odds ratio of 1.37 between groups (CI = 0.9-2.09; p = 0.14) and stroke/neurological complications, 1.59 (CI = 0.96-2.63; p = 0.07). CONCLUSION: In cardiac surgery patients, transfusion of pRBCs closer to end of shelf-life was not shown to be associated with significantly increased mortality or morbidity. Dose-dependent differences in adverse outcomes (particularly where units transfused were > 4) were supported.

Management of massive haemorrhage in transfusion medicine services in the Middle East and North Africa.

BACKGROUND AND OBJECTIVES: Massive transfusion protocols (MTPs) are critical in managing haemorrhage, yet their utilization varies. There is lack of data on the utilization of MTPs in the Middle East and North Africa (MENA) region. This study aims to assess the degree of utilization of MTPs in the region. MATERIALS AND METHODS: We conducted a survey to collect data on MTP use, inviting medical directors of transfusion services from various hospitals. Data were analysed to determine the prevalence of MTP utilization, their compositions, challenges in application and areas of future need. RESULTS: Eighteen respondents participated, representing 11 countries in the region. Thirteen hospitals implemented MTP, and eight included paediatrics. Eleven institutions used more than one definition of massive haemorrhage, with the most common being ≥10 red blood cell (RBC) units transfused for adults and replacement of >50% total blood volume in paediatrics. The majority of sites with MTPs utilized 1:1:1 RBCs:platelets:plasma ratio (70%). Variations were observed in the types and blood groups of components used. Two sites utilized whole blood, while six are considering it for future use. Utilization of adjunctive agents and frequency of laboratory testing varied among the sites. Challenges included the lack of medical expertise in protocol development, adherence and paediatric application. The need assessment emphasized the need for developing regional guidelines, standardized protocols and training initiatives. CONCLUSION: Although several hospitals have adopted MTPs, variations exist in activation criteria, blood product ratios and monitoring. Challenges include the lack of medical expertise, protocol adherence and addressing paediatric needs. Standardizing protocols, enhancing training and paediatric application are crucial for improving massive transfusion management in the region.

Bioaccessibility of bioactive compounds from Pereskia aculeata and their cellular antioxidant effect.

Ora-pro-nobis (Pereskia aculeata) is a Cactaceae plant with edible leaves and fruits whose extracts are consumed to promote health, albeit bioactive compounds' bioaccessibility was still not assessed. To address this, ora-pro-nobis fruits (FE) and leaf extracts (LE) were subjected to in vitro digestion to better understand how this process impacts the bioactivities of the extracts. The study investigated the composition of the extracts, their cytotoxicity, and their chemical, plasmatic, and cellular antioxidant capacity. The results revealed that total polyphenolics were about 70% bioaccessible in LE and FE, with phenylalanine being the most bioaccessible essential amino acid in leaves (42.7%) and fruits (83.6%). The samples' antioxidant activity (CUPRAC) was reduced by 25%. LE demonstrated antioxidant activity against human plasma oxidation and haemolysis (21.8%), but digestion mitigated these activities. FE diminished haemolysis (47.0%) and presented cytotoxicity (IC50 = 1086 µg/mL) to HUVEC cells, but these properties were lost following digestion. Ultimately, digestion partially degraded the samples' bioactive compounds, diminishing their cellular protection against oxidative stress.

Internalization of nano- and micro-plastics in human erythrocytes leads to oxidative stress and estrogen receptor-mediated cellular responses.

Plastic material versatility has resulted in a substantial increase in its use in several sectors of our everyday lives. Consequently, concern regarding human exposure to nano-plastics (NPs) and micro-plastics (MPs) has recently increased. It has been shown that plastic particles entering the bloodstream may adhere to the erythrocyte surface and exert adverse effects following erythrocyte aggregation and adhesion to blood vessels. Here, we explored the effects of polystyrene nano-plastics (PS-NPs) and micro-plastics (PS-MPs) on human erythrocytes. Cellular morphology, binding/internalization of PS-NPs and PS-MPs, oxidative stress parameters, as well as the distribution and anion exchange capability of band 3 (anion exchanger 1; SLC4A1) have been analyzed in human erythrocytes exposed to 1 µg/mL PS-NPs or PS-MPs for 3 and 24 h, respectively. The data obtained showed significant modifications of the cellular shape after exposure to PS-NPs or PS-MPs. In particular, a significantly increased number of acanthocytes, echinocytes and leptocytes were detected. However, the percentage of eryptotic cells (<1 %) was comparable to physiological conditions. Analytical cytology and confocal microscopy showed that PS-NPs and PS-MPs bound to the erythrocyte plasma membrane, co-localized with estrogen receptors (Erα/ERß), and were internalized. An increased trafficking from the cytosol to the erythrocyte plasma membrane and abnormal distribution of ERs were also observed, consistent with ERα-mediated binding and internalization of PS-NPs. An increased phosphorylation of ERK1/2 and AKT kinases indicated that an activation of the ER-modulated non-genomic pathway occurred following exposure to PS-NPs and PS-MPs. Interestingly, PS-NPs or PS-MPs caused a significant production of reactive oxygen species, resulting in an increased lipid peroxidation and protein sulfhydryl group oxidation. Oxidative stress was also associated with an altered band 3 ion transport activity and increased oxidized haemoglobin, which led to abnormal clustering of band 3 on the plasma membrane. Taken together, these findings identify cellular events following the internalization of PS-NPs or PS-MPs in human erythrocytes and contribute to elucidating potential oxidative stress-related harmful effects, which may affect erythrocyte and systemic homeostasis.

Luspatercept enhances hemoglobin levels in a Chinese boy with congenital sideroblastic anemia: A case report.

BACKGROUND: Congenital sideroblastic anemia (CSA) is a rare and heterogeneous group of genetic disorders. Conventional treatment include pyridoxine (vitamin B6) and allogeneic hematopoietic stem cell transplantation (allo-HSCT), and can alleviate anemia in the majority of cases. Nevertheless, some CSA cases remain unresponsive to pyridoxine or are unable to undergo allo-HSCT. Novel management approaches is necessary to be developed. To explore the response of luspatercept in treating congenital sideroblastic anemia. CASE SUMMARY: We share our experience in luspatercept in a 4-year-old male patient with CSA. Luspatercept was administered subcutaneously at doses of 1.0 mg/kg/dose to 1.25 mg/kg/dose every 3 wk, three consecutive doses, evaluating the hematological response. Luspatercept leading to a significant improvement in the patient's anemia. The median hemoglobin during the overall treatment with three doses of luspatercept was 90 (75-101) g/L, the median absolute reticulocyte count was 0.0593 (0.0277-0.1030) × 1012/L, the median serum ferritin was 304.3 (234.4-399) ng/mL, and the median lifespan of mature red blood cells was 80 (57-92) days. Notably, no adverse reactions, such as headaches, dizziness, vomiting, joint pain, or back pain, were observed during the treatment period. CONCLUSION: We believe that luspatercept might emerge as a viable therapeutic option for the maintenance treatment of CSA or as a bridging treatment option before hematopoietic stem cell transplantation.

Investigation of the efficacy and safety of wild- type and triple-gene knockout pig RBC transfusions in nonhuman primates.

Introduction: Decreasing rates of blood donation and close margins between blood supply and demand pose challenges in healthcare. Genetically engineered pig red blood cells (pRBCs) have been explored as alternatives to human RBCs for transfusion, and triple-gene knockout (TKO) modification improves the compatibility of pRBCs with human blood in vitro. In this study, we assessed the efficacy and risks of transfusing wild-type (WT)- and TKO-pRBCs into nonhuman primates (NHPs). Methods: Blood from O-type WT and TKO pigs was processed to produce pRBCs for transfusion, which were transfused or not into NHPs (n=4 per group: WT, TKO, and control) after 25% total blood volume withdrawal: their biological responses were compared. Hematological, biochemical, and immunological parameters were measured before, immediately after, and at intervals following transfusion. Two months later, a second transfusion was performed in three NHPs of the transfusion group. Results: Transfusion of both WT- and TKO-pRBCs significantly improved RBC counts, hematocrit, and hemoglobin levels up to the first day post-transfusion, compared to the controls. The transfusion groups showed instant complement activation and rapid elicitation of anti-pig antibodies, as well as elevated liver enzyme and bilirubin levels post-transfusion. Despite the higher agglutination titers with WT-pRBCs in the pre-transfusion crossmatch, the differences between the WT and TKO groups were not remarkable except for less impairment of liver function in the TKO group. After the second transfusion, more pronounced adverse responses without any hematological gain were observed. Conclusions: WT- and TKO-pRBC transfusions effectively increased hematologic parameters on the first day, with rapid clearance from circulation thereafter. However, pRBC transfusion triggers strong antibody responses, limiting the benefits of the pRBC transfusion and increasing the risk of adverse reactions.

Impact of Different Red Blood Cell Storage Solutions and Conditions on Cell Function and Viability: A Systematic Review.

Red blood cell (RBC) storage solutions have evolved significantly over the past decades to optimize the preservation of cell viability and functionality during hypothermic storage. This comprehensive review provides an in-depth analysis of the effects of various storage solutions and conditions on critical RBC parameters during refrigerated preservation. A wide range of solutions, from basic formulations such as phosphate-buffered saline (PBS), to advanced additive solutions (ASs), like AS-7 and phosphate, adenine, glucose, guanosine, saline, and mannitol (PAGGSM), are systematically compared in terms of their ability to maintain key indicators of RBC integrity, including adenosine triphosphate (ATP) levels, morphology, and hemolysis. Optimal RBC storage requires a delicate balance of pH buffering, metabolic support, oxidative damage prevention, and osmotic regulation. While the latest alkaline solutions enable up to 8 weeks of storage, some degree of metabolic and morphological deterioration remains inevitable. The impacts of critical storage conditions, such as the holding temperature, oxygenation, anticoagulants, irradiation, and processing methods, on the accumulation of storage lesions are also thoroughly investigated. Personalized RBC storage solutions, tailored to individual donor characteristics, represent a promising avenue for minimizing storage lesions and enhancing transfusion outcomes. Further research integrating omics profiling with customized preservation media is necessary to maximize post-transfusion RBC survival and functions. The continued optimization of RBC storage practices will not only enhance transfusion efficacy but also enable blood banking to better meet evolving clinical needs.

Engineering of Erythrocytes as Drug Carriers for Therapeutic Applications.

Erythrocytes, also known as red blood cells (RBCs), have garnered considerable attention as potential carriers for drug delivery, owing to their inherent properties such as biocompatibility, biodegradability, and prolonged circulation half-life. This paper presents a comprehensive overview of the role of erythrocytes in drug delivery, elucidating recent advancements in delivering a diverse array of therapeutic agents, including small molecules, nucleic acids, antibodies, protein enzymes, and nanoparticles. Two primary strategies for encapsulating drugs within erythrocytes are systematically discussed: internal loading and surface loading. Each strategy offers distinct advantages in terms of drug stability and release kinetics. Notably, the utilization of erythrocyte membrane camouflaged nanocarriers holds promise for enhancing the biocompatibility of conventional nanoparticles and facilitating targeted drug delivery. Furthermore, the broad spectrum of biomedical applications of erythrocyte-based drug delivery systems are examined, ranging from cancer treatment to diabetes management, thrombosis prevention, and immunotherapy. This review provides a comprehensive evaluation of current technologies in erythrocyte-loaded drug delivery, highlighting the strengths, weaknesses, and future directions for advancing therapeutic interventions in various disease contexts.

Differences in endothelial function between patients with Type 1 and Type 2 diabetes: effects of red blood cells and arginase.

The mechanisms underlying endothelial dysfunction in Type 1 and Type 2 diabetes (T1DM and T2DM) are unresolved. The red blood cells (RBCs) with increased arginase activity induce endothelial dysfunction in T2DM, but the implications of RBCs and the role of arginase inhibition in T1DM are unexplored. We aimed to investigate the differences in endothelial function in patients with T1DM and T2DM, with focus on RBCs and arginase. Thirteen patients with T1DM and twenty-six patients with T2DM, matched for HbA1c and sex were included. In vivo endothelium-dependent and -independent vasodilation (EDV and EIDV) were assessed by venous occlusion plethysmography before and after administration of an arginase inhibitor. RBCs were co-incubated with rat aortic segments for 18h followed by evaluation of endothelium-dependent (EDR) and -independent relaxation (EIDR) in isolated organ chambers. In vivo EDV, but not EIDV, was significantly impaired in patients with T2DM compared with patients with T1DM. Arginase inhibition resulted in improved EDV only in T2DM. RBCs from patients with T2DM induced impaired EDR but not EIDR in isolated aortic segments, whereas RBCs from patients with T1DM did not affect EDR nor EIDR. The present study demonstrates markedly impaired EDV in patients with T2DM in comparison with T1DM. In addition, it highlights the divergent roles of RBCs and arginase in mediating endothelial dysfunction in T1DM and T2DM. While endothelial dysfunction is mediated via RBCs and arginase in T2DM, these phenomena are not prominent in T1DM thereby indicating distinct differences in underlying mechanisms.

Red blood cells based nanotheranostics: A smart biomimetic approach for fighting against cancer.

The technique of engineering drug delivery vehicles continues to develop, which bring enhancements in working more efficiently and minimizing side effects to make it more effective and safer. The intense capability of therapeutic agents to remain undamaged in a harsh extracellular environment is helpful to the success of drug development efforts. With this in mind, alterations of biopharmaceuticals with enhanced stability and decreased immunogenicity have been an increasingly active focus of such efforts. Red blood cells (RBCs), also known as erythrocytes have undergone extensive scrutiny as potential vehicles for drug delivery due to their remarkable attributes over the years of research. These include intrinsic biocompatibility, minimal immunogenicity, flexibility, and prolonged systemic circulation. Throughout the course of investigation, a diverse array of drug delivery platforms based on RBCs has emerged. These encompass genetically engineered RBCs, non-genetically modified RBCs, and RBC membrane-coated nanoparticles, each devised to cater to a range of biomedical objectives. Given their prevalence in the circulatory system, RBCs have gained significant attention for their potential to serve as biomimetic coatings for artificial nanocarriers. By virtue of their surface emulation capabilities and customizable core materials, nanocarriers mimicking these RBCs, hold considerable promise across a spectrum of applications, spanning drug delivery, imaging, phototherapy, immunomodulation, sensing, and detection. These multifaceted functionalities underscore the considerable therapeutic and diagnostic potential across various diseases. Our proposed review provides the synthesis of recent strides in the theranostic utilization of erythrocytes in the context of cancer. It also delves into the principal challenges and prospects intrinsic to this realm of research. The focal point of this review pertains to accentuating the significance of erythrocyte-based theranostic systems in combating cancer. Furthermore, it precisely records the latest and the most specific methodologies for tailoring the attributes of these biomimetic nanoscale formulations, attenuating various discoveries for the treatment and management of cancer.

Assessing the impact of severe acute respiratory syndrome coronavirus 2 infection on hematological parameters.

BACKGROUND: The current study is a retrospective study designed to evaluate changes in complete blood count and coagulation parameters in adult coronavirus disease 2019 (COVID-19) patients at a prominent Saudi tertiary center to predict disease severity and mortality. METHODS: The cohort consisted of 74 800 adult patients divided into four groups based on a COVID-19 test and the patient's sex: 35 985 in the female negative COVID-19 group, 23 278 in the male negative COVID-19 group, 8846 in the female positive COVID-19 group and 6691 in the male positive COVID-19 group. RESULTS: Patients with COVID-19 demonstrated decreased white blood cell counts and increased red blood cell counts. Also, COVID-19-positive participants exhibited more prolonged partial thromboplastin time and lower D-dimer levels than those of COVID-19-negative subjects (p<0.05). The study also revealed gender-dependent impacts on platelet counts, implying a possible relationship with the greater infection mortality rate in men than in women (p<0.001). In addition, the study found a link between changes in coagulation test results and death in COVID-19 patients (p<0.001). The evidence regarding the effects of COVID-19 on blood cell counts and coagulation, on the other hand, is conflicting, most likely due to variances in study populations and the timing of testing postinfection. CONCLUSIONS: According to the findings, COVID-19-related alterations in blood cell count and clotting ability may be risk factors for death.