Trileucine is utilized as a source of leucine for growth of strains of Escherichia coli K-12 that are deficient in the oligopeptide transport system. Leu-Leu and Leu-Leu-Leu have been utilized to formulate spray-dried pulmonary formulations with improved aerosol performance (dispersibility) and stability. Trileucine's low aqueous solubility enables the formation of low-density corrugated particles and promotes the formation of trileucine coated spray-dried particles, resulting in superior aerosol performance. Trileucine is surface active and promotes the formation of spray-dried powders with a reduced cohesiveness as demonstrated by a decrease in the measured surface energy which correlates with an observed improvement in aerosol performance. Additionally, trileucine competes with the protein on the air/water interface resulting in an additional depression of surface tension in solution which correlates with a decreased denaturation and aggregation in the solid state. The incorporation of trileucine (3 Leu) residues as an endo-osmolytic moiety in the peptide improves endosomal escape and intracellular delivery of siRNA. The trileucine motif did not affect early non-endosomal mechanism of cytoplasmic siRNA delivery but enhanced target gene silencing by >20% only beyond 24 h of transfection when siRNA delivery is mostly through the endocytic route and siRNA trapped in the endosomes at later stages were subject to release into cytoplasm. The mechanism may involve endosomal membrane disruption as trileucine residues lysed RBCs selectively under endosomal pH conditions. Trileucine is efficiently utilized when infused intravenously (IV) in baboons who are fed a complete diet orally.