Hemolysate-filled polyethyleneimine and polyurea microcapsules as potential red blood cell substitutes: effect of aqueous monomer type on properties of the prepared microcapsules


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Abstract

In this paper, we describe the synthesis and characterization of rabbit hemolysate-filled polyethyleneimine (PEI)- or polyurea (PU)-type artificial red blood cells (ARBCs) with different membrane compositions. These microcapsules were prepared by making use of the interfacial polymerization (IP) reaction between the water-soluble amine monomers (triethylamine (TEA), ethylene glycol-bis(β-aminoethyl ether)-N,N′-tetraacetic acid (EGATA), diethylenetriamine (DETA), tetramethyl diaminomethane (TMDAM), piperazine hexahydrate (PPHH), l-lysine monohydrochloride (LLMH) or PEI) and 2,4-toluylene diisocyanate (TDI) as an oil-soluble shell monomer. The resultant microcapsules were spherical and with mean diameters of 8.71–63.33 μm. Microcapsules having sulfonic acid groups on their surfaces were prepared by using a combination of the functional amines (DETA, LLMH or PEI) and 4,4′-diaminostilbene-2,2′-disulfonic acid (DASSA). Oxygen-binding abilities of the ARBCs were measured by a Clark-type oxygen electrode. The obtained results revealed that the highest oxygen-binding abilities were obtained with the PU-ARBCs prepared with DETA alone or in combination with EGATA. Unfortunately, these microcapsules exhibited large diameters and wider size distribution curves (span values (S)=1.3, 1.7, geometric standard deviation (σg)=1.85, 2.18, respectively). However, the novel ARBCs (sulfonated PU-PEI graft copolymer membrane microcapsules (SPU/PEI-ARBCs)) prepared had good oxygen affinity, the smallest mean diameter (d=8.71 μm) and the best distribution (S=0.9, σg=1.48) and a flow behavior identical to rabbit RBCs. Therefore, these unique microcapsules can be recommended for scale-up considerations as a promising blood substitute.

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