Premium
Biological Evaluation of Liposome‐Encapsulated Hemoglobin Surface‐Modified With a Novel PEG ylated Nonphospholipid Amphiphile
Author(s) -
Yadav Vivek R.,
Nag Okhil,
Awasthi Vibhudutta
Publication year - 2014
Publication title -
artificial organs
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.684
H-Index - 76
eISSN - 1525-1594
pISSN - 0160-564X
DOI - 10.1111/aor.12304
Subject(s) - amphiphile , liposome , hemoglobin , pegylation , chemistry , materials science , biomedical engineering , nanotechnology , polyethylene glycol , biochemistry , organic chemistry , medicine , copolymer , polymer
Abstract Traumatic injury is often associated with hemorrhagic shock. Liposome‐encapsulated hemoglobin ( LEH ) is being developed as an artificial oxygen carrier to address post‐hemorrhage oxygen and volume deficit. Here, we report a new composition of LEH based on the use of polyethylene glycol ( PEG 2K ) conjugated with nonphospholipid hexadecylcarbamoylmethylhexadecanoate ( HDAS ) to modify the surface of LEH particles. LEH was manufactured by the high‐pressure homogenization method using dipalmitoylphosphatidylcholine (∼38 mol%), cholesterol (∼38 mol%), HDAS (∼20 mol%), and highly purified stroma‐free human hemoglobin. HDAS ‐ PEG 2K was postinserted into the resultant LEH to generate HDAS ‐ PEG 2K ‐ LEH . We investigated the potential immune response to HDAS ‐ PEG 2K ‐ LEH in a mice model. At the same time, the preparation was tested in a rat model to study the effect of repeated HDAS ‐ PEG 2K ‐ LEH injection over 4 weeks. We found that HDAS ‐ PEG 2K modification substantially reduced the circulating levels of anaphylatoxins C 3a and C 5a, as well as plasma levels of thromboxane B 2, in mice. Repeated injections of HDAS ‐ PEG 2K ‐ LEH in rats did not appear to alter its clearance profile after 4 weeks of treatment. No antibody response against human hemoglobin or PEG was detected in rat plasma. Histological observations of lung, liver, spleen, and kidney were not significantly different between saline‐treated rats and HDAS ‐ PEG 2K ‐ LEH ‐treated rats. Immunohistochemical staining for rat heme oxygenase‐1 ( HO ‐1) did not show induced expression of HO ‐1 in these organs. These results suggest that the new surface modification of LEH is immune‐neutral and does not adversely affect histology even after repeated administration.