Glutaraldehyde modified red blood cells delivering artesunate to the liver as a dual therapeutic and prophylactic antimalaria strategy.

Malaria can spread quickly in the population and develop rapidly. Patients with malaria usually die due to lack of timely and effective treatment. Artesunate (AS) is a highly effective and low-toxicity antimalarial drug, but its short half-life in the blood makes it difficult to control the malaria infection completely. Red blood cells (RBCs) have great biodegradability and can be employed to encapsulate various drugs. In this work, we employed RBCs as carriers to encapsulate AS and modified them with glutaraldehyde to construct an intelligent response drug delivery system (G-AS-RBCs) targeting the liver for antimalaria therapeutic and prophylactic activity. The G-AS-RBCs had a drug loading amount of 6.56 ± 0.14 mg 10-8 cells, suggesting excellent biocompatibility. G-AS-RBCs exhibited strong liver targeting efforts and can be maintained in the mice for at least 9 days, showing the potential for malaria prevention. The enrichment of AS in the liver was enhanced because of the natural liver targeting of erythrocytes and the enhancement of liver targeting by glutaraldehyde treatment. Furthermore, AS entrapped into RBCs also showed improved slow-release characteristics and achieved a better effect of inhibiting or killing the malaria parasite than free drugs. Therefore, this RBC-based strategy is expected to realize the prevention and treatment of malaria and has good application prospects.

Blood cell-based drug delivery systems: A biomimetic platform for antibacterial therapy.

With the rapid increase in multidrug-resistance against antibiotics, higher doses of antibiotics or more effective antibiotics are needed to treat diseases, which ultimately leads to a decrease in the body's immunity and seriously threatens human health worldwide. The efficiency of antibiotics has been a large challenge for years. To overcome this problem, many carriers are utilized for anti-bacteria, attempting to optimize the delivery of such drugs and transport them safely and directly to the site of disease. Blood cell-based drug delivery systems present several advantages as compared to polymeric delivery system. These blood cells including red blood cells (RBCs), leukocytes, platelets. The blood cells and their membranes can both be used as drug carriers to deliver antibacterial drugs. In addition, blood cells can overcome many physiological/pathological obstacles faced by nanoparticles in vivo and effectively deliver drugs to the site of the disease. In this paper, we review studies on blood cell-based delivery systems used in antibacterial therapy, and analyze different roles in antibacterial therapy, which provide basis for further study in this field.

Red Blood Cell Membrane-Camouflaged Tedizolid Phosphate-Loaded PLGA Nanoparticles for Bacterial-Infection Therapy.

Multiple drug resistance (MDR) in bacterial infections is developed with the abuse of antibiotics, posing a severe threat to global health. Tedizolid phosphate (TR-701) is an efficient prodrug of tedizolid (TR-700) against gram-positive bacteria, including methicillin-sensitive staphylococcus aureus (MSSA) and methicillin-resistant staphylococcus aureus (MRSA). Herein, a novel drug delivery system: Red blood cell membrane (RBCM) coated TR-701-loaded polylactic acid-glycolic acid copolymer (PLGA) nanoparticles (RBCM-PLGA-TR-701NPs, RPTR-701Ns) was proposed. The RPTR-701Ns possessed a double-layer core-shell structure with 192.50 ± 5.85 nm in size, an average encapsulation efficiency of 36.63% and a 48 h-sustained release in vitro. Superior bio-compatibility was confirmed with red blood cells (RBCs) and HEK 293 cells. Due to the RBCM coating, RPTR-701Ns on one hand significantly reduced phagocytosis by RAW 264.7 cells as compared to PTR-701Ns, showing an immune escape effect. On the other hand, RPTR-701Ns had an advanced exotoxins neutralization ability, which helped reduce the damage of MRSA exotoxins to RBCs by 17.13%. Furthermore, excellent in vivo bacteria elimination and promoted wound healing were observed of RPTR-701Ns with a MRSA-infected mice model without causing toxicity. In summary, the novel delivery system provides a synergistic antibacterial treatment of both sustained release and bacterial toxins absorption, facilitating the incorporation of TR-701 into modern nanotechnology.

Clinical progress and advanced research of red blood cells based drug delivery system.

Red blood cells (RBCs) are biocompatible carriers that can be employed to deliver different bioactive substances. In the past few decades, many strategies have been developed to encapsulate or attach drugs to RBCs. Osmotic-based encapsulation methods have been industrialized recently, and some encapsulated RBC formulations have reached the clinical stage for treating tumors and neurological diseases. Inspired by the intrinsic properties of intact RBCs, some advanced delivery strategies have also been proposed. These delivery systems combine RBCs with other novel systems to further exploit and expand the application of RBCs. This review summarizes the clinical progress of drugs encapsulated into intact RBCs, focusing on the loading and clinical trials. It also introduces the latest advanced research based on developing prospects and limitations of intact RBCs drug delivery system (DDS), hoping to provide a reference for related research fields and further application potential of intact RBCs based drug delivery system.