FORMATION OF HIGH AXIAL-RATIO MICROSTRUCTURES FROM PEPTIDES MODIFIED WITH GLUTAMIC-ACID DIALKYL AMIDES

A growing number of amphiphiles are known to form high axial ratio mic rostructures (HARMs) such as the hollow cylindrical microstructures ca lled lipid tubules, As a prelude to exploring the potential of HARMs f ormed from lipopeptides in controlled release drug delivery, several m icrostructure formation conditions were investigated. We report the pr eparation of several glutamic acid dialkyl amides with varying alkyl c hain lengths bearing a variety of peptides (1-4 amino acids) [peptide- Glu-(NHCnH2n+1)(2), n = 12, 14, 16]. These surfactants have been rapid ly and efficiently converted into HARMs in aqueous buffer at physiolog ical pH and ionic strength, or in buffer containing MeOH or EtOH. Heli cal ribbons and tubular HARMs were produced that were stable for as lo ng as 6 months below the phase transition temperatures of the compound s. To estimate the stability of HARMs in vivo, HARMs formed from (Pro) (3)-Glu(NHC16H33)(2) were incubated with DOPC liposomes or fetal calf serum at 40 degrees C. HARM size and shape did not change significantl y, suggesting that such lipopeptide particles can retain their morphol ogy long enough in vivo to be useful as drug delivery vehicles. (C) 19 98 Elsevier Science B.V. All rights reserved.