Liposomes as Potential Carrier for Bioactive β2,2- Amino Acid Derivatives - A Feasibility Study

Abstract

The emergence of antibiotic resistant bacterial strains is a rising global problem that does not only result in fatal infections of previously treatable cases, but increases also the economic burden of health care systems. The same applies for cancer as treatment of some cancer types is difficult and also resistance to treatment is an increasing problem in cancer chemotherapy. Novel treatment approaches are needed and so called antimicrobial and anticancer peptides were identified as promising new weapons against pathogenic bacteria and cancer cells. We demonstrated in our earlier studies that these β2,2-amino acid derivatives possess antimicrobial and anticancer activities when tested in vitro.. As part of the drug development process it is also crucial to find appropriate carrier systems for these derivatives, preferably at an early developmental stage. In this study we evaluated liposomes as potential drug carriers for β2,2-amino acid derivatives and investigated the interaction of the incorporated derivatives with liposomes. The β2,2-amino acid derivatives A2, A3 and A6 were synthesized, characterized and then A2 and A3 were incorporated into liposomes which were prepared by the film hydration method. Entrapment efficiencies of about 70 % were obtained for the non-sonicated liposomes and about 40 % for sonicated liposomes. Size determination revealed sizes of around 1000 nm for the non-sonicated liposomes and sizes under 100 nm after 1 min sonication. The pronounced and fast decrease in liposome size is an indication that the derivatives affect the fluidity of the liposome membranes. Zeta potential measurements showed surface charges of up to +37 mV. These findings suggest a possible effect of the derivatives on charge of the liposomes, which are composed of neutral soy phosphatidylcholine. Further studies are needed to evaluate the impact of the positive surface charge and the release properties of the liposomes. The determined entrapment efficiencies as well as liposome properties indicate that liposomes have the potential for being used as drug carriers for β2,2-amino acid derivatives.