Methemoglobin-albumin clusters for the treatment of hydrogen sulfide intoxication

Pharmaceutical Integrity of Lyophilized Methemoglobin-Albumin Clusters after Reconstitution

“…shifted to slightly lower values, with an increased PD-index and ζ-potential compared to control (Figure d, Table ). In our previous study, metHb-albumin clusters were found to be composed of one metHb with several molecules of HSA ( n = 2–5) on the surface connected by lysine groups of metHb and Cys-34 of HSA by a heterobifunctional cross-linker . The diameter of hemoglobin-albumin clusters is reported to decrease from 14.8 to 9.5 nm as the number of HSA molecules conjugated to hemoglobin decreases from 4 to 1 .…”

“…The results indicate that metHb in lyophilized metHb-albumin clusters retained an active ferric heme center after reconstitution. Ferric iron in metHb has a high binding affinity for H 2 S, with the result that metHb-albumin clusters detoxify H 2 S . As heme released from heme proteins is a source of oxidative stress resulting in tissue damages, − it is important to avoid release of free heme, so the stability shown for metHb in the clusters represents an important safety observation.…”

“…The is comparable to that for metHb-albumin clusters without lyophilization and reconstitution. 10 However, in the glucose F.D. group, one model mouse (out of eight) was not rescued (Figure 5).…”

“…metHb-albumin clusters (5 g metHb/dL in PBS, pH 7.4) were prepared, as reported previously. 10 4.2. Lyophilization and Reconstitution of metHb-Albumin Clusters.…”

“…metHb-albumin clusters have recently been developed as a promising antidote for hydrogen sulfide (H 2 S) poisoning . metHb-albumin clusters are composed of a metHb core covalently bound to human serum albumin (HSA) molecules via a bifunctional cross-linker (Figure ).…”