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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. [ABSTRACT FROM AUTHOR]

Red blood cells (RBCs) can act as carriers for therapeutic agents and can substantially improve the safety, pharmacokinetics, and pharmacodynamics of many drugs. Maintaining RBCs integrity and lifespan is important for the efficacy of RBCs as drug carrier. We investigated the impact of drug encapsulation by hypotonic dialysis on RBCs physiology and integrity. Several parameters were compared between processed RBCs loaded with l-asparaginase (“eryaspase”), processed RBCs without drug and non-processed RBCs. Processed RBCs were less hydrated and displayed a reduction of intracellular content. We observed a change in the metabolomic but not in the proteomic profile of processed RBCs. Encapsulation process caused moderate morphological changes and was accompanied by an increase of RBCs-derived Extracellular Vesicles release. Despite a decrease in deformability, processed RBCs were not mechanically retained in a spleen-mimicking device and had increased surface-to-volume ratio and osmotic resistance. Processed RBCs half-life was not significantly affected in a mouse model and our previous phase 1 clinical study showed that encapsulation of asparaginase in RBCs prolonged its in vivo half-life compared to free forms. Our study demonstrated that encapsulation by hypotonic dialysis may affect certain characteristics of RBCs but does not significantly affect the in vivo longevity of RBCs or their drug carrier function.

Red blood cells (RBCs) can act as carriers for therapeutic agents and can substantially improve the safety, pharmacokinetics, and pharmacodynamics of many drugs. Maintaining RBCs integrity and lifespan is important for the efficacy of RBCs as drug carrier. We investigated the impact of drug encapsulation by hypotonic dialysis on RBCs physiology and integrity. Several parameters were compared between processed RBCs loaded with l -asparaginase ("eryaspase"), processed RBCs without drug and non-processed RBCs. Processed RBCs were less hydrated and displayed a reduction of intracellular content. We observed a change in the metabolomic but not in the proteomic profile of processed RBCs. Encapsulation process caused moderate morphological changes and was accompanied by an increase of RBCs-derived Extracellular Vesicles release. Despite a decrease in deformability, processed RBCs were not mechanically retained in a spleen-mimicking device and had increased surface-to-volume ratio and osmotic resistance. Processed RBCs half-life was not significantly affected in a mouse model and our previous phase 1 clinical study showed that encapsulation of asparaginase in RBCs prolonged its in vivo half-life compared to free forms. Our study demonstrated that encapsulation by hypotonic dialysis may affect certain characteristics of RBCs but does not significantly affect the in vivo longevity of RBCs or their drug carrier function. A wide red blood cell (RBC) characterization demonstrated that ERYCAPS® hypotonic dialysis encapsulation process induces some changes to RBC features without substantially affecting their survival or their capacity to carry therapeutics. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: This study aims to formulate and characterize sorafenib-loaded resealed erythrocytes (SoRE) and investigate their anticancer activity in a rat model of hepatocellular carcinoma., Methods: SoRE were prepared by hypotonic dialysis of red blood cells obtained from Wistar rats using a range of drug-containing dialysis mediums (2-10 mg/ml) and osmosis time (30-240 mins). Optimized SoRE (8 mg/mL and 240 mins) were characterized for size, morphology, stability, entrapment efficiency, in vitro release profiles, and in vivo efficacy evaluations. For efficacy studies, optimized SoRE were intravenously administered to Wistar rats having hepatocellular lesions induced by aflatoxin B and monitored for in vivo antineoplastic activity., Results: The amount of sorafenib entrapped was directly proportional to the drug concentration in the dialysis medium and duration of osmosis; highest for 10 mg/mL and 240 minutes and lowest for 2 mg/mL and 30 minutes, respectively. Optimized SoRE were biconcave with a size of 112.7 nm and zeta potential of -11.95 ± 2.25 mV. Osmotic and turbulence fragility were comparable with native erythrocytes., Conclusion: Drug release follows the first-order pattern. In vivo investigations reveal better anticancer activity of SoRE formulation compared to sorafenib standard preparation. Resealed erythrocytes loaded with sorafenib displayed first-order in vitro release and promising anticancer activity in a rat model of hepatocellular carcinoma., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)