Synthetic Erythrocytes

Djordjevich, Ljubomir; Mayoral, Jorge W.; Ivankovich, Anthony D.

doi:10.1097/00000542-198509001-00109

Cited by 9 publications

(3 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Significant research has been performed to formulate Hb-based artificial blood for the treatment of hypoxia, hemorrhagic shock, and tissue oxygenation. 23,24 In systemic administration of artificial blood, Hb is readily oxygenated in the lung and unloads oxygen in tissues. When Hb in the cross-linked form of Hb-C is present in the microcapsules, oxygen transport to islets by the entrapped Hb may rely on a facilitated oxygen transport mechanism.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Effect of Cross-Linked Hemoglobin on Functionality and Viability of Microencapsulated Pancreatic Islets

2002

View full text Add to dashboard Cite

Of many obstacles involved in developing a bioartificial pancreas, which consists of encapsulated and physically immunoprotected islets, for long-term implantation in insulin-dependent diabetic patients, the impaired functionality and decreasing viability of encapsulated islets over time are critical factors in determining the size and longevity of the implant. These factors are closely associated with short oxygen supply to the encaged islets from the implant site. To facilitate oxygen transport to islets in the capsules, we coencapsulated hemoglobin cross-linked with difunctional polyethylene glycol (Hb-conjugate, Hb-C) which is large in size (>100 kDa), thus preventing diffusional loss through the immunoprotecting membrane. The coencapsulation of Hb-C with islets in alginate-poly-L-lysine microcapsules by dissolving Hb-C in an islet-suspended alginate solution at a concentration of 0.25 mM improved the insulin secretion and viability of the islets. At week 0, the islets, coencapsulated with Hb-C, cultured at P(O2) = 40 mmHg (assumed oxygen partial pressure in the most common implant site, the peritoneal cavity), secreted 200% more insulin compared with the control islets without Hb-C at glucose concentrations of both 100 and 300 mg/dL. The Hb-C effect became more significant with time at higher glucose concentrations. After culturing the islets for 8 weeks at 40 mmHg, the insulin secretion was enhanced 200 and 550% at glucose concentrations of 100 and 300 mg/dL as compared with the control, respectively. The results were closely associated with improved viability and suggest that the introduction of Hb-C is an effective approach to maintaining the oxygen supply to encapsulated islets. In addition, Hb-C coencapsulation with pancreatic islets may (1) provide a partial clue to reducing the large size of the biohybrid artificial pancreas, (2) lead to a reduced need for pancreas donation, and (3) prolong the longevity of the biohybrid artificial pancreas in the body.

show abstract

Section: Discussionmentioning

confidence: 99%

“…23,24 In this study, the effects of cross-linked Hb on the functionality and viability of microencapsulated islets of Langerhans were investigated. Fresh oxy-Hb was isolated from human red blood cells and conjugated with a nontoxic water-soluble polymer of PEG.…”

Section: Introductionmentioning

confidence: 99%

Effect of Cross-Linked Hemoglobin on Functionality and Viability of Microencapsulated Pancreatic Islets

2002

View full text Add to dashboard Cite

show abstract

“…In contrast, encapsulation of Hb may improve these disadvantages, as encapsulation would decrease vasoconstriction and NO scavenging by Hb (6,7). Liposome‐encapsulated Hb (LEH) was studied as an AOC, as it was thought that Hb should also be encapsulated like red blood cells (RBCs) (8–10). Nonetheless, issues particular to liposome preparations such as the complex manufacturing process, low encapsulation efficiency causing increased production costs, and instability of manufactured products and liposome themselves have hampered development.…”

mentioning

confidence: 99%

Liposome‐Encapsulated Hemoglobin, TRM‐645: Current Status of the Development and Important Issues for Clinical Application

et al. 2009

View full text Add to dashboard Cite

Clinical application of artificial oxygen carriers as a substitute for blood transfusion has long been expected to solve some of the problems associated with blood transfusion. Use for oxygen delivery treatment for ischemic disease by oxygen delivery has also been examined. These prospective applications of artificial oxygen carriers are, however, still in development. We have developed liposome-encapsulated hemoglobin (LEH), developmental code TRM-645, using technologies for encapsulation of concentrated hemoglobin (Hb) with high encapsulation efficiency as well as surface modification to achieve stability in circulating blood and a long shelf life. We have confirmed the basic efficacy and safety of TRM-645 as a red blood cell substitute in studies on the efficacy of oxygen delivery in vivo, and the safety of TRM-645 has been studied in some animal species. We are now examining various issues related to clinical studies, including further preclinical studies, management of manufacturing and the quality assurance for the Hb solution and liposome preparations manufactured by the GMP facility.

show abstract

Blood, Artificial

Winslow¹

2000

Kirk-Othmer Encyclopedia of Chemical Technology

View full text Add to dashboard Cite

Artificial blood is herein defined as consisting of red cell substitutes. Red cell substitutes are solutions intended for use in patients whose red cells are either not available or their use is to be avoided for other reasons. Despite enormous effort, more than 100 years of research have not produced a solution that can be used safely in humans. Hemoglobin can exist in either of two structural conformations, corresponding to the oxy ( R , relaxed) or deoxy ( T , tense) states. The key differences between these two structures are that the constrained T state has a much lower oxygen affinity than the R state and the T state has a lower tendency to dissociate into subunits that can be filtered in the kidneys. Therefore, stabilization of the T conformation would be expected to solve both the oxygen affinity and renal excretion problems. The clinical consequences of stabilization are not known. Differences in the reactions considered to be useful in the production of hemoglobin‐based blood substitutes are determined by the dimensions and reactivity of the cross‐linking reagents. Even small differences among structures of the reagents can yield products having very different properties. In addition, the conditions of the reaction are very important, not only in regard to the state of ligation, ie, oxygen saturation, but also in regard to the presence of agents or molecules that block or compete for certain reactive sites. It has been difficult to produce a pure modified hemoglobin for toxicity studies because most processes start with relatively crude, stroma‐free hemoglobin. Hemoglobin is provided by the red blood cell in highly purified form. However, red cell membranes contain many components that could potentially cause toxicity problems. Furthermore, plasma proteins and other components could cause toxic reactions in recipients of hemoglobin preparations. Rabiner's method for the filtration purification of hemoglobin was thought to be a significant advance over older centrifugation methods. However, hemoglobin prepared in this way still caused unwanted reactions in human recipients. If clinical efficacy and safety of hemoglobin solutions can be shown, the demand for product would soon outstrip the supply of outdated human blood. One solution to the hemoglobin supply problem is to use as a starting material blood from nonhuman sources. For example, bovine hemoglobin is being developed for use. The ultimate success of bovine, or any other hemoglobin, depends on demonstration of safety, not on supply. One problem in using bovine hemoglobin is the fear of bovine spongiform encephalitis (BSE) virus. The FDA is concerned about bovine products of all types. An alternative and novel source of hemoglobin for modification is from microorganisms the genome of which has been modified to contain globin genes for recombinant hemoglobin (rHb) production. Significant strides have been made in this approach. Several of the products discussed herein are under intense development. One product, based on recombinant hemoglobin, was in early human trials as of this writing. Other hemoglobin‐based solutions are also under review at the FDA.

show abstract

Synthetic Erythrocytes

Cited by 9 publications

References 0 publications

Effect of Cross-Linked Hemoglobin on Functionality and Viability of Microencapsulated Pancreatic Islets

Effect of Cross-Linked Hemoglobin on Functionality and Viability of Microencapsulated Pancreatic Islets

Liposome‐Encapsulated Hemoglobin, TRM‐645: Current Status of the Development and Important Issues for Clinical Application

Blood, Artificial

Contact Info

Product

Resources

About