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Biological Evaluation of Liposome‐Encapsulated Hemoglobin Surface‐Modified With a Novel PEGylated Nonphospholipid Amphiphile

Traumatic injury is often associated with hemorrhagic shock. Liposome‐encapsulated hemoglobin () is being developed as an artificial oxygen carrier to address post‐hemorrhage oxygen and volume deficit. Here, we report a new composition of based on the use of polyethylene glycol () conjugated with no... Full description

Journal Title: Artificial Organs August 2014, Vol.38(8), pp.625-633
Main Author: Yadav, Vivek R.
Other Authors: Nag, Okhil , Awasthi, Vibhudutta
Format: Electronic Article Electronic Article
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ID: ISSN: 0160-564X ; E-ISSN: 1525-1594 ; DOI: 10.1111/aor.12304
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recordid: wj10.1111/aor.12304
title: Biological Evaluation of Liposome‐Encapsulated Hemoglobin Surface‐Modified With a Novel PEGylated Nonphospholipid Amphiphile
format: Article
creator:
  • Yadav, Vivek R.
  • Nag, Okhil
  • Awasthi, Vibhudutta
subjects:
  • Oxygen Delivery
  • Liposome‐Encapsulated Hemoglobin
  • Complement
ispartof: Artificial Organs, August 2014, Vol.38(8), pp.625-633
description: Traumatic injury is often associated with hemorrhagic shock. Liposome‐encapsulated hemoglobin () is being developed as an artificial oxygen carrier to address post‐hemorrhage oxygen and volume deficit. Here, we report a new composition of based on the use of polyethylene glycol () conjugated with nonphospholipid hexadecylcarbamoylmethylhexadecanoate () to modify the surface of particles. was manufactured by the high‐pressure homogenization method using dipalmitoylphosphatidylcholine (∼38 mol%), cholesterol (∼38 mol%), (∼20 mol%), and highly purified stroma‐free human hemoglobin. ‐ was postinserted into the resultant to generate ‐‐. We investigated the potential immune response to ‐‐ in a mice model. At the same time, the preparation was tested in a rat model to study the effect of repeated ‐‐ injection over 4 weeks. We found that ‐ modification substantially reduced the circulating levels of anaphylatoxins 3a and 5a, as well as plasma levels of thromboxane 2, in mice. Repeated injections of ‐‐ in rats did not appear to alter its clearance profile after 4 weeks of treatment. No antibody response against human hemoglobin or was detected in rat plasma. Histological observations of lung, liver, spleen, and kidney were not significantly different between saline‐treated rats and ‐‐‐treated rats. Immunohistochemical staining for rat heme oxygenase‐1 (‐1) did not show induced expression of ‐1 in these organs. These results suggest that the new surface modification of is immune‐neutral and does not adversely affect histology even after repeated administration.
language:
source:
identifier: ISSN: 0160-564X ; E-ISSN: 1525-1594 ; DOI: 10.1111/aor.12304
fulltext: fulltext
issn:
  • 0160-564X
  • 0160564X
  • 1525-1594
  • 15251594
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titleBiological Evaluation of Liposome‐Encapsulated Hemoglobin Surface‐Modified With a Novel PEGylated Nonphospholipid Amphiphile
creatorYadav, Vivek R. ; Nag, Okhil ; Awasthi, Vibhudutta
ispartofArtificial Organs, August 2014, Vol.38(8), pp.625-633
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subjectOxygen Delivery ; Liposome‐Encapsulated Hemoglobin ; Complement
descriptionTraumatic injury is often associated with hemorrhagic shock. Liposome‐encapsulated hemoglobin () is being developed as an artificial oxygen carrier to address post‐hemorrhage oxygen and volume deficit. Here, we report a new composition of based on the use of polyethylene glycol () conjugated with nonphospholipid hexadecylcarbamoylmethylhexadecanoate () to modify the surface of particles. was manufactured by the high‐pressure homogenization method using dipalmitoylphosphatidylcholine (∼38 mol%), cholesterol (∼38 mol%), (∼20 mol%), and highly purified stroma‐free human hemoglobin. ‐ was postinserted into the resultant to generate ‐‐. We investigated the potential immune response to ‐‐ in a mice model. At the same time, the preparation was tested in a rat model to study the effect of repeated ‐‐ injection over 4 weeks. We found that ‐ modification substantially reduced the circulating levels of anaphylatoxins 3a and 5a, as well as plasma levels of thromboxane 2, in mice. Repeated injections of ‐‐ in rats did not appear to alter its clearance profile after 4 weeks of treatment. No antibody response against human hemoglobin or was detected in rat plasma. Histological observations of lung, liver, spleen, and kidney were not significantly different between saline‐treated rats and ‐‐‐treated rats. Immunohistochemical staining for rat heme oxygenase‐1 (‐1) did not show induced expression of ‐1 in these organs. These results suggest that the new surface modification of is immune‐neutral and does not adversely affect histology even after repeated administration.
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descriptionTraumatic injury is often associated with hemorrhagic shock. Liposome‐encapsulated hemoglobin () is being developed as an artificial oxygen carrier to address post‐hemorrhage oxygen and volume deficit. Here, we report a new composition of based on the use of polyethylene glycol () conjugated with nonphospholipid hexadecylcarbamoylmethylhexadecanoate () to modify the surface of particles. was manufactured by the high‐pressure homogenization method using dipalmitoylphosphatidylcholine (∼38 mol%), cholesterol (∼38 mol%), (∼20 mol%), and highly purified stroma‐free human hemoglobin. ‐ was postinserted into the resultant to generate ‐‐. We investigated the potential immune response to ‐‐ in a mice model. At the same time, the preparation was tested in a rat model to study the effect of repeated ‐‐ injection over 4 weeks. We found that ‐ modification substantially reduced the circulating levels of anaphylatoxins 3a and 5a, as well as plasma levels of thromboxane 2, in mice. Repeated injections of ‐‐ in rats did not appear to alter its clearance profile after 4 weeks of treatment. No antibody response against human hemoglobin or was detected in rat plasma. Histological observations of lung, liver, spleen, and kidney were not significantly different between saline‐treated rats and ‐‐‐treated rats. Immunohistochemical staining for rat heme oxygenase‐1 (‐1) did not show induced expression of ‐1 in these organs. These results suggest that the new surface modification of is immune‐neutral and does not adversely affect histology even after repeated administration.
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abstractTraumatic injury is often associated with hemorrhagic shock. Liposome‐encapsulated hemoglobin () is being developed as an artificial oxygen carrier to address post‐hemorrhage oxygen and volume deficit. Here, we report a new composition of based on the use of polyethylene glycol () conjugated with nonphospholipid hexadecylcarbamoylmethylhexadecanoate () to modify the surface of particles. was manufactured by the high‐pressure homogenization method using dipalmitoylphosphatidylcholine (∼38 mol%), cholesterol (∼38 mol%), (∼20 mol%), and highly purified stroma‐free human hemoglobin. ‐ was postinserted into the resultant to generate ‐‐. We investigated the potential immune response to ‐‐ in a mice model. At the same time, the preparation was tested in a rat model to study the effect of repeated ‐‐ injection over 4 weeks. We found that ‐ modification substantially reduced the circulating levels of anaphylatoxins 3a and 5a, as well as plasma levels of thromboxane 2, in mice. Repeated injections of ‐‐ in rats did not appear to alter its clearance profile after 4 weeks of treatment. No antibody response against human hemoglobin or was detected in rat plasma. Histological observations of lung, liver, spleen, and kidney were not significantly different between saline‐treated rats and ‐‐‐treated rats. Immunohistochemical staining for rat heme oxygenase‐1 (‐1) did not show induced expression of ‐1 in these organs. These results suggest that the new surface modification of is immune‐neutral and does not adversely affect histology even after repeated administration.
doi10.1111/aor.12304
pages625-33
date2014-08