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 microstructures (HARMs) such as the hollow cylindrical microstructures called lipid tubules. As a prelude to exploring the potential of HARMs formed from lipopeptides in controlled release drug delivery, several microstructure formation conditions were investigated. We report the preparation of several glutamic acid dialkyl amides with varying alkyl chain lengths bearing a verity of peptides (1-4 amino acids) [peptide-Glu-(NHCnH2n+1)2, n=12, 14, 16]. These surfactants have been rapidly and efficiently converted into HARMs in aqueous buffer at physiological pH and ionic strength, or in buffer containing MeOH or EtOH. Helical ribbons and tubular HARMs were produced that were stable for as long as 6 months below the phase transition temperatures of the compounds. 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 degreesC. HARM size and shape did not change significantly, suggesting that such lipopeptide particles can retain their morphology long enough in vivo to be useful as drug delivery vehicles.