Inclusion of ganglioside GM1 into liposome encapsulated hemoglobin does not extend circulation persistence at clinically relevant doses.
This investigation has evaluated the substitution of ganglioside GM1 for dimyristoyl phosphatidylglycerol (DMPG) in the preparation of liposome encapsulated hemoglobin (LEH), with the intention of increasing the circulation persistence of this potential oxygen carrier. Although equivalent yields of each formulation were produced by microfluidization, the hemoglobin encapsulation efficiency was greater for GM1-LEH than DMPG-LEH. Similar particle sizes, phospholipid content, methemoglobin levels, and oxygen-carrying capacity were observed for both formulations. Zeta potential measurements to monitor liposomal surface charge showed GM1-LEH to be more electropositive than DMPG-LEH. Using differential scanning calorimetry, similar enthalpy values and hemoglobin structural transition temperatures were determined for both LEH formulations. Circulation persistence of each LEH formulation was determined following a 0.25 ml (1 g phospholipid/Kg body weight) or 0.5 ml (2 g phospholipid/Kg body weight) injection in mice. During the first 18 hours, GM1-LEH was cleared at a faster rate than DMPG-LEH at both dosages studied. Then the remaining liposomes of each formulation were removed with identical circulation profiles until no liposomes were remaining in circulation at either 50 hours (0.25 ml) or 72 hours (0.5 ml) post-injection. These data reveal that the use of ganglioside GM1 to solely increase the circulation persistence of LEH was of little benefit.
Goins
B
B
Center for Biomolecular Science and Engineering, Naval Research Laboratory, Washington, D.C. 20375-5000.
Ligler
F S
FS
Rudolph
A S
AS
D000818:Animals; D001803:Blood Transfusion; D004337:Drug Carriers; D004359:Drug Therapy, Combination; D005260:Female; D005677:G(M1) Ganglioside / Q000008:administration & dosage*; D006207:Half-Life; D006454:Hemoglobins / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D008955:Models, Cardiovascular; D010100:Oxygen / Q000097:blood; D010715:Phosphatidylglycerols / Q000008:administration & dosage; D051381:Rats; D013997:Time Factors
D004337:Drug Carriers; D006454:Hemoglobins; D008081:Liposomes; D010715:Phosphatidylglycerols; D005677:G(M1) Ganglioside; C002773:dimyristoylphosphatidylglycerol; D010100:Oxygen