Probiotics: potential pharmaceutical applications.

Natural cells have been explored as drug carriers for a long period. They have received growing interest as a promising drug delivery system (DDS) until recently along with the development of biology and medical science. The synthetic materials, either organic or inorganic, are found to be with more or less immunogenicity and/or toxicity. The cells and extracellular vesicles (EVs), are endogenous and thought to be much safer and friendlier. Furthermore, in view of their host attributes, they may achieve different biological effects and/or targeting specificity, which can meet the needs of personalized medicine as the next generation of DDS. In this review, we summarized the recent progress in cell or cell membrane-based DDS and their fabrication processes, unique properties and applications, including the whole cells, EVs and cell membrane coated nanoparticles. We expect the continuing development of this cell or cell membrane-based DDS will promote their clinic applications.

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Cell or Cell Membrane-Based Drug Delivery Systems

Importance of the field: Vascular delivery of several classes of therapeutic agents may benefit from carriage by red blood cells (RBC), for example, drugs that require delivery into phagocytic cells and those that must act within the vascular lumen. The fact that several protocols of infusion of RBC-encapsulated drugs are now being explored in patients illustrates a high biomedical importance for the field.Areas covered by this review: Two strategies for RBC drug delivery are discussed: encapsulation into isolated RBC ex vivo followed by infusion in compatible recipients and coupling therapeutics to the surface of RBC. Studies of pharmacokinetics and effects in animal models and in human studies of diverse therapeutic enzymes, antibiotics and other drugs encapsulated in RBC are described and critically analyzed. Coupling to RBC surface of compounds regulating immune response and complement, affinity ligands, polyethylene glycol alleviating immune response to donor RBC and fibrinolytic plasminogen activato...

Drug delivery by red blood cells: vascular carriers designed by mother nature

A great majority of the Ru complexes currently studied in anticancer research exert their antiproliferative activity, at least partially, through ligand exchange. In recent years, however, coordinatively saturated and substitutionally inert polypyridyl Ru(II) compounds have emerged as potential anticancer drug candidates. In this work, we present the synthesis and detailed characterization of two novel inert Ru(II) complexes, namely, [Ru(bipy)2(Cpp-NH-Hex-COOH)]2+ (2) and [Ru(dppz)2(CppH)]2+ (3) (bipy = 2,2′-bipyridine; CppH = 2-(2′-pyridyl)pyrimidine-4-carboxylic acid; Cpp-NH-Hex-COOH = 6-(2-(pyridin-2-yl)pyrimidine-4-carboxamido)hexanoic acid; dppz = dipyrido[3,2-a:2′,3′-c]phenazine). 3 is of particular interest as it was found to have IC50 values comparable to cisplatin, a benchmark standard in the field, on three cancer cell lines and a better activity on one cisplatin-resistant cell line than cisplatin itself. The mechanism of action of 3 was then investigated in detail and it could be demonstrated t...

Molecular and Cellular Characterization of the Biological Effects of Ruthenium(II) Complexes Incorporating 2-Pyridyl-2-pyrimidine-4-carboxylic Acid

Cell-based drug delivery.

Purpose. The aim of this work was to encapsulate recombinant human erythropoietin (rHuEpo) in human and mouse red blood cells (RBCs) to improve the stability of encapsulated rHuEpo. 
Methods. The encapsulation of rHuEpo was achieved by an hypotonic dialysis-isotonic resealing procedure. A radioimmunoassay method was used for the estimation of rHuEpo. The hypoosmotic resistance of carrier erytrhocytes was studied by osmotic fragility measurements. Cell morphology was observed under scanning electron microscopy. Encapsulated rHuEpo was identified by an immunogold labeling assay. 
Results. Encapsulation yields were 22% for human RBCs and 14% for mouse RBCs. Cell recovery was around 70%. Carrier-RBCs exhibited a tendency to spherocytic morphology, and showed the typical higher hypoosmotic resistance than normal RBCs. The presence of rHuEpo inside carrier RBCs was identified. The stability of encapsulated rHuEpo seems to be related to the experimental conditions used during the encapsulation procedure. An increase with time of released rHuEpo was observed in carrier-RBC suspensions. 
Conclusions. The encapsulation of rHuEpo in RBCs has been achieved for the first time. These carrier RBC-preparations may serve as an alternative sustained cell delivery system for the in vivo administration of rHuEpo.

Erythrocytes as Carriers for Recombinant Human Erythropoietin

In vitro study of alcohol dehydrogenase and acetaldehyde dehydrogenase encapsulated into human erythrocytes by an electroporation procedure

Mouse erythrocytes as carriers for coencapsulated alcohol and aldehyde dehydrogenase obtained by electroporation in vivo survival rate in circulation, organ distribution and ethanol degradation.

Montserrat Pinilla

Papers

Erythrocytes as Carriers for Recombinant Human Erythropoietin

In vitro study of alcohol dehydrogenase and acetaldehyde dehydrogenase encapsulated into human erythrocytes by an electroporation procedure

Mouse erythrocytes as carriers for coencapsulated alcohol and aldehyde dehydrogenase obtained by electroporation in vivo survival rate in circulation, organ distribution and ethanol degradation.

In vitro and in vivo study of glutamate dehydrogenase encapsulated into mouse erythrocytes by a hypotonic dialysis procedure.

Effects of the antitumoural dequalinium on NB4 and K562 human leukemia cell lines. Mitochondrial implication in cell death.