Conjugation of methoxypolyethylene glycol to the surface of bovine red blood cells

Abstract

Methoxypolyethylene glycol (mPEG) covalently bound to the surface of human red blood cells (hRBCs) has been shown to decrease immunological recognition of hRBC surface antigens (Bradley et al., 2002). However, there is an increasing shortage of hRBC donations, thus making hRBCs scarce and expensive (Davey, 2004; Riess, 2001). The goal of this study is to similarly PEGylate the surface of bovine RBCs (bRBCs) with the aim of reducing the demand on human blood donations needed for blood transfusions. This study investigates the feasibility of modifying the surface of bRBCs with the succinimidyl ester of methoxypolyethylene glycol propionic acid (SPA-mPEG) for use as a potential blood substitute. The oxygen binding affinity of PEGylated bRBCs was moderately increased with increasing initial SPA-mPEG concentrations up to 4 mM when reacted with bRBCs at a hematocrit of 12%. Oxygen transport simulations verified that SPA-mPEG conjugated bRBCs could still transport oxygen to pancreatic islet tissues even under extreme conditions. PEGylated bRBCs reconstituted to a hematocrit of 40% exhibited viscosities on the order of approximately 3 cp, similar to hRBCs at the same hematocrit. Taken together, the results of this study demonstrate the success of PEGylating bRBCs to yield modified cells with oxygen binding, transport and flow properties similar to that of hRBCs.

Mathematical model of NO and O2 transport in an arteriole facilitated by hemoglobin based O2 carriers

“…Generally, the O 2 transfer rate follows the trend described in previous studies [38, 39] with maximal O 2 transfer occurring at a target pO 2 region close to each HBOC’s respective P 50 value. The P 50 represents the point on the O 2 equilibrium curve with the greatest slope; thus a small change in the pO 2 in this region results in a large change in the fractional saturation of the HBOC, Figure 1.…”

Targeted O2 delivery by blood substitutes: in vitro arteriolar simulations of first- and second-generation products

“…To apply this method, other investigators have modeled tissue O 2 metabolism using Michaelis-Menton kinetics as given in Eq. 9 (Dimino and Palmer, 2007; Gundersen and Palmer, 2007; Patton and Palmer, 2006). $$M_t=\frac{V_{\max }p}{K_m+p}$$ In this, M t is the local rate of O 2 consumption, V max is the maximal rate, and K m is the p O 2 where M t = 0.5V m .…”

“…A number of studies have quantified O 2 transport from RBCs or RBC/HBOC mixtures for individual capillaries (Dimino and Palmer, 2007; Gundersen and Palmer, 2007; Patton and Palmer, 2006; Vadapalli et al, 2002) and for microvascular networks (Sharan and Popel, 2002; Tsoukias et al, 2007). To date, no study has quantitatively addressed the potentially large difference in arteriolar O 2 transport for the particular combination of these three commercially developed HBOCs, particularly since MP4 is a recently introduced product.…”

Efficacy of pretreatment of allografts with methoxypolyethylene glycol-succinimidyl-propionic acid ester in combination with an anti-OX40L monoclonal antibody in relieving graft-versus-host disease in mice

“…It has no toxicity or immunogenicity and does not accumulate in the human body or affect the biological functions of its substrates [4,5]. Additionally, mPEG and its derivative, mPEG-succinimidyl-propionic acid ester (mPEG-SPA) are two commonly used chemical modifiers that have been approved by the FDA for clinical use [4].…”