Engineering erythrocytes as a novel carrier for the targeted delivery of the anticancer drug paclitaxel

Abstract

Paclitaxel (PTX) is formulated in a mixture of Cremophor EL and dehydrated alcohol. The intravenous administration of this formula is associated with a risk of infection and hypersensitivity reactions. The presence of Cremophor EL as a pharmaceutical vehicle contributes to these effects. Therefore, in this study, we used human erythrocytes, instead of Cremophor, as a pharmaceutical vehicle. PTX was loaded into erythrocytes using the preswelling method. Analysis of the obtained data indicates that 148.8 lg of PTX was loaded/mL erythrocytes, with an entrapment efficiency of 46.36% and a cell recovery of 75.94%. Furthermore, we observed a significant increase in the mean cell volume values of the erythrocytes, whereas both the mean cell hemoglobin and the mean cell hemoglobin concentration decreased following the loading of PTX. The turbulence fragility index values for unloaded, sham-loaded and PTX-loaded erythrocytes were 3, 2, and 1 h, respectively. Additionally, the erythrocyte glutathione level decreased after PTX loading, whereas lipid peroxidation and protein oxidation increased. The release of PTX from loaded erythrocytes followed first-order kinetics, and about 81% of the loaded drug was released into the plasma after 48 h. The results of the present study revealed that PTX was loaded successfully into human erythrocytes with acceptable loading parameters and with some oxidative modification to the erythrocytes.ª 2013 Production and hosting by Elsevier B.V. on behalf of King Saud University.

On Command Drug Delivery via Cell‐Conveyed Phototherapeutics

“…Finally, we note that the maximum tolerated dose of docetaxel injected intravenously to mice is ≈250 µg per mouse (10 mg kg −1 ) . Typical dosage for treatment in mice is anywhere between 75 µg per mouse for low dosage up to the experimental maximum tolerated dose for high dosage . In contrast, the sum total TAX content in the transfused mRBCs is only 1 µg per mouse.…”

The use of erythrocyte fragility to assess xenobiotic cytotoxicity

“…However, the activation of apoptosis highlights, as for the nucleated cells, the toxicity of various xenobiotics against these cells. Furthermore, erythrocyte membranes from different species of mammal can be used, not only as a model system but also as a carrier for diverse active substance vehicles . Animal experimentation is more informative than experimentation, but there are major ethical and financial limitations to the approach.…”

“…Furthermore, erythrocyte membranes from different species of mammal can be used, not only as a model system but also as a carrier for diverse active substance vehicles. 50,51 Animal experimentation is more informative than experimentation, but there are major ethical and financial limitations to the approach. Therefore, in vitro assays represent an alternative method to testing; indeed, in vitro experiments are often used as an initial screen for the toxicity of substances, the evaluation of their cytotoxic mechanisms and the alternative testing methods to replace animal experimentation that the pharmaceutical scientist may use as a guide to assess the safety and utility of a parenteral formulation.…”

Autologous erythrocytes delivery of berberine hydrochloride with long-acting effect for hypolipidemia treatment

“…The whole blood was collected from rats by orbital plexus vein and transferred into a tube with heparin sodium for anticoagulation. Then centrifuged at 4 C, 600Âg for 3 min to remove the plasma and leukocytes in the supernatant, and washed three times with 5% isotonic glucose solution at 4 C. A pre-swelling method was used for loading BH into RBCs (Harisa et al, 2014). 100 lL washed packed RBCs were added to 1 mL hypotonic drug solution (5.2 mg/mL NaHCO 3 , 2.5 mg/mL BH after heating), incubated at room temperature for 20 min.…”