Improved biological properties of synthetic distearoyl phosphatidyl choline-based liposome in the conscious rat.
We have previously produced and tested a liposome preparation based on hydrogenated soy lecithin (HSL-L) for the purpose of designing blood replacement in the form of liposome encapsulated hemoglobin (LEH). While these liposomes had acceptable physicochemical properties which addressed many of the desirable characteristics of "artificial blood," they produced hypotension, hemoconcentration, and thrombocytopenia when administered to rats. The following studies present improved synthetic distearoyl phosphatidylcholine-based liposomes (sDSPC-L) which were compared to the HSL-L for their biological effects in the conscious normovolemic rat (n = 6 - 11). HSL-L induced hypotension (-25 +/- 3 mmHg, P less than 0.01), tachycardia (+88 +/- 11 beats/min, P less than 0.01), decrease in cardiac index (-33 +/- 4%, P less than 0.01), and elevation of the total peripheral resistance index (+0.450 +/- 0.003 mmHg/ml/min/kg, P less than 0.01). The hematologic responses to HSL-L were: leukocytosis (+6,070 +/- 1,064/microliters, P less than 0.01), hemoconcentration (+4.0 +/- 0.1%, P less than 0.01), 0.01), and thrombocytopenia (-160 +/- 18 X 10(3)/microliters, P less than 0.01). Plasma thromboxane B2 (TXB2) was elevated to 30.4 +/- 5.6 pg/100 microliters (P less than 0.01). In contrast, the only effects induced by sDSPC-L were slight tachycardia (+37 +/- 9 beats/min, P less than 0.05) and a marginal increase in plasma TXB2 to 9.7 +/- 3.3 pg/100 microliters (P less than 0.05). All effects, except for those related to cardiac output and peripheral resistance, were transient. These data underscore the importance of pure synthetic DSPC in improving the biological effects of liposomes and suggest sDSPC-L as a promising vehicle for encapsulating hemoglobin.
Rabinovici
R
R
Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
Rudolph
A S
AS
Feuerstein
G
G
D000818:Animals; D001772:Blood Cell Count / Q000187:drug effects; D001802:Blood Substitutes / Q000494:pharmacology*; D004337:Drug Carriers; D006439:Hemodynamics / Q000187:drug effects; D006454:Hemoglobins / Q000008:administration & dosage; D008081:Liposomes; D010713:Phosphatidylcholines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D001802:Blood Substitutes; D004337:Drug Carriers; D006454:Hemoglobins; D008081:Liposomes; D010713:Phosphatidylcholines; C010942:1,2-distearoyllecithin