Stability of poly(Acrylic Acid)-grafted phospholipid liposomes in gastrointestinal conditions

Major limitations in the use of liposomes for oral formulation relate to their physical and chemical instability in the GI tract. In this study, the conjugate (PAA‐DSPE) of poly(acrylic acid) and distearoylphosphatidylethanolamine (DSPE) was synthesized, and liposomes were prepared with the mixture of PAA‐DSPE and DSPE to improve the stability of liposomes in the GI tract. The prepared PAA‐DSPE was characterized by FT‐IR and 13C‐NMR to confirm the coupling between PAA and DSPE. In the elemental analysis, the coupling ratio of PAA and DSPE in PAA‐DSPE was calculated as 1:1.73. The average size of a PAA‐DSPE/DSPE liposome, measured by dynamic light scattering, was in the range of 300–500 nm, and the minimum average size was 320 nm at 6 mol% of PAA‐DSPE. The stability of the prepared liposomes was evaluated in different pH (2, 5, 7.4) solutions, and in different concentrations of bile acid (0, 0.1, 1, 10%) and pancreatin solutions (0, 0.03, 0.3, 3%). The stability of liposomes in different conditions was determined by measuring the fluorescence intensity of 5(6)‐CF leaked from liposomes. The amount of the 5(6)‐CF leakage from the PAA‐DSPE/DSPE liposomes of 6 mol% PAA‐DSPE was the lowest in all the cases of acidic, bile, and pancreatin solutions. In conclusion, the optimum amount of PAA‐DSPE in liposome was 6 mol%, and PAA‐DSPE/DSPE liposomes could improve the stability in the GI tract. Drug Dev. Res. 61:13–18, 2004. © 2004 Wiley‐Liss, Inc.