DEXTRAN FATTY-ACID ESTERS AS POLYMERIC SURFACTANTS WITH LOW HEMOLYTIC-ACTIVITY

Practically all low molecular weight surfactants show hemolytic activi ties. Aside of this serious disadvantage,almost all low molecular weig ht solubilizers cause considerable side effects, particularly during o r after parenteral application. Polymeric surfactants, however, usuall y show no or only very little hemolytic effects. They therefore are su pposed not to be able to penetrate neither into cellular or erythrocyt e walls nor into phospholipid bilayers, resp.,similar bilayer membrane s due to their large molecular size. Therefore no decay of biological bilayers should be expected with polymeric surfactants. The only pharm aceutically widely used polymeric surfactants are at the moment polyox yethylene-polyoxypropylene block copolymers (poloxamers (INN), Pluroni cs(R) and Pluriols(R)). Unfortunately they have only poor solubility c apacities. In order to find better solubilizing polymeric surfactants, some water soluble dextran fatty acid esters (Ref. 1) were synthesize d and tested with respect to their solubilisation capacity and hemolyt ic activity. Usually the hemolytic activity is tested by standard meth ods using purified animal or human erythrocyte suspensions. As erythro cytes also contain a relatively high amount of lactose dehydrogenase ( LDH), we studied the suitability of the highly sensitive, and in the m edical diagnostic well known LDH test, as a supplemental hemolytic det ermination method (Ref. 2). The advantage of this test is, that there is no need of the time consuming purification and standardization as i t is required with the erythrocytes' suspension. It can be performed w ith original blood and without costly preparations at all. The synthes ized dextran fatty acid esters proved themselves as very little hemoly tic and, compared with the polyoxyethylene-polyoxypropylene block copo lymers, they show improved solubilisation capacities.