Physicochemical properties of microemulsion analogues of low density lipoprotein containing amphiphatic apoprotein B receptor sequences

Low density lipoprotein (LDL) has been proposed as a drug targeting vector in cancer chemotherapy, however. research has been limited due to the neces sity to isolate material from plasma. In this study, the physicochemical pr operties of synthetic lipid microemulsions containing an amphiphatic versio n of the apoprotein B receptor binding sequence have been examined. The eff ect of peptide sequence length. lipid anchor type and location along with m icroemulsion lipid composition were investigated via changes in particle si ze and zeta potential. Size increases were related to the amphiphatic pepti des lipophilic portion and too a lesser extent by amino acid sequence lengt h. Two lipophilic anchors, retinoic acid and cholesterol. produced large si ze increases whilst. a single anchor (retinoic acid) did not affect size. T he amphiphatic peptide reversed measured zeta potential from negative to po sitive values in a concentration dependent manner. This was related to pept ide structure and could be effected by changes in pH, indicating that the p eptide was surface located and responsive to the external environment. Alte ration of microemulsion lipid composition also affected physicochemical pro perties but to a lesser degree than changes in the amphiphatic peptide, The se novel systems may represent a useful synthetic alternative to native LDL for a variety of applications. (C) 2001 Elsevier Science B.V. All rights r eserved.