The stability of heparin-coated liposomes in plasma and their effect on its coagulation

The potential use of liposomes as drug carriers is still limited by their poor stability under storage conditions and in biological systems. To improve their stability and blood compatibility, positively, neutral and negatively charged large unilamellar vesicles were coated with heparin. As expected, addition of heparin to a positively charged phosphatidylcholine/cholesterol/stearylamine mixed micellar solution or preformed liposomes, resulted in rapid liposome aggregation. On the contrary, no aggregation was observed with heparin and neutral or negatively charged lipid components of mixed micelles or liposome bilayers. No heparin release from the heparin-coated liposomes was observed during prolonged incubation of the liposome carrier with buffer and human plasma. The results indicate that, compared with conventional liposomes, the stability of heparin-coated liposomes was significantly increased. This was even more effective when dicetylphosphate, a negatively charged lipid, was included in the liposome structure.