Long term safety and immunological effects of a nanobiotherapeutic, bovine poly-[hemoglobin-catalase-superoxide dismutase-carbonic anhydrase], after four weekly 5% blood volume top-loading followed by a challenge of 30% exchange transfusion

Abstract

The long-term safety and immunological effects of bovine poly-[haemoglobin-catalase-superoxide dismutase-carbonic anhydrase] in rats are studied by four-weekly 5% blood volume top-loading infusions followed by 30% blood volume exchange transfusion. There is no significant difference in growth, biochemistry and blood pressure between the control group receiving lactated ringer solution and those receiving the bovine poly-[haemoglobin-catalase-superoxide dismutase-carbonic anhydrase]. There is no significant change in mean arterial pressures (MAP) before and after each weekly top-loading infusion. After both the four weekly top-loading and the 30% exchange transfusions, the following safety and immune response evaluations are carried out. These include general studies on Ouchterlony double diffusion, total IgG and IgM, and complement activation. This is followed by quantitative measurements of specific antibodies against each of the following bovine components: Hb, CAT, SOD and CA in bovine poly-[haemoglobin-catalase-superoxide dismutase-carbonic anhydrase]. After the four weekly top-loading, each rat received a challenge of 30% blood volume exchange transfusion. The MAP, histamine and tryptase levels are tested before and after the 30% exchange transfusion. There are no anaphylactic reactions as shown by the MAP or histamine and tryptase. The results showed no safety problem nor adverse immune responses. All the rats survived when followed for one week after the 30% exchange transfusion.

A polymer–lipid membrane artificial cell nanocarrier containing enzyme–oxygen biotherapeutic inhibits the growth of B16F10 melanoma in 3D culture and in a mouse model

“…Decreasing the molecular weight of the polylactide would increase the rate of biodegradation of the polymer. The content of PH-TYR will be metabolized like another of our enzyme-oxygen therapeutic poly-[haemoglobin-catalase-superoxide dismutase-carbonic anhydrase] that did not show any safety or immunological problem [21] and is now under development for clinical trial.…”

ARTIFICIAL CELL evolves into nanomedicine, biotherapeutics, blood substitutes, drug delivery, enzyme/gene therapy, cancer therapy, cell/stem cell therapy, nanoparticles, liposomes, bioencapsulation, replicating synthetic cells, cell encapsulation/scaffold, biosorbent/immunosorbent haemoperfusion/plasmapheresis, regenerative medicine, encapsulated microbe, nanobiotechnology, nanotechnology

“…contaminated donor blood. It is only then that intense R&D on blood substitutes was belatedly carried out around the world [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35]. It was found out too late that blood substitute requires the same long-term research as in any other medical research for cancer and other diseases.…”

“…Our result in a 90 min haemorrhagic shock animal model with 2/3 blood volume loss ( Figure 10) [29] shows that it is superior to whole blood in the following ways: lowering of elevated intracellular pCO 2 , recovery of ST elevation, tropronin levels, lowering of elevated lactate, histology of the heart and intestine. Long term study of bovine PolyHb-SOD-CAT-CA in rats shows safety and lack of immunological problems after 4 weekly 5% blood volume infusion followed by 30% volume exchange transfusion [32]. This includes the measurement of histamine and tryptase that show no anaphylactic reaction ( Figure 10).…”

“…Figure 7 Enzymes inside artificial cells can act on external permeant substrates while avoiding protein sensitization, anaphylactic reaction, or antibody production with repeated injection [2][3][4]6,8,9] (Figure 13). Chang's groups has been investigating the use of artificial cells for enzyme therapy since 1964 [2][3][4][5][6][7][8][9][10]25,26,[29][30][31][32][33][51][52][53][54][55] (Figure 13).…”

“…Lower left: Test for anaphylactic reaction: no significant increase in tryptase nor histamine. Above figures from Chang's group[29,32,36].…”