dipalmitoylphosphatidylserine and 1-2-distearoyllecithin

The kinetics and thermodynamics of lipid flip-flop in bilayers composed of 1,2-dipalmitoyl-sn-glycero-3-phospho-L-serine (DPPS) and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) were studied using sum-frequency vibrational spectroscopy. The kinetics of DSPC and DPPS flip-flop were examined as a function of temperature and bilayer composition. The rate of DSPC flip-flop did not exhibit any significant dependence on bilayer composition while the rate of DPPS flip-flop was inversely dependent on the mole fraction of DPPS. The transition-state thermodynamics for DSPC and DPPS lipids in these mixed bilayers were determined in order to identify the energetic impact of the phosphatidylserine headgroup on lipid flip-flop. The thermodynamics for the DSPC component remained statistically identical to bilayers composed entirely of DSPC. The activation energy for the DPPS component showed a linear correlation with the mole fraction of DPPS for all bilayer compositions. The enthalpy and entropy for DPPS flip-flop did not increase linearly with the fraction of DPPS but did directly correlate with the molecular area. The DPPS component also exhibited enthalpy-entropy compensation which suggests that lipid hydration may play a significant role in membrane dynamics.

Topics: Kinetics; Lipid Bilayers; Phosphatidylcholines; Phosphatidylserines; Spectrum Analysis; Thermodynamics; Vibration

In order to evaluate the usefulness of liposomes, which are stable in acidic solution, bile and pancreatin solution (stable liposomes), as vehicle for oral vaccines, the intestinal IgA antibody responses of mice to liposome-associated antigen after oral administration were examined. The intestinal IgA antibody responses against ganglioside GM1 were detected after the oral immunization of ganglioside GM1-containing stable liposomes. When monophosphoryl lipid A was incorporated into stable liposomes containing ganglioside GM1, further augmentation of IgA responses to ganglioside GM1 was observed. On the other hand, the oral administration with ganglioside GM1 alone was unable to induce any detectable intestinal anti-ganglioside GM1 IgA antibody response. These results suggest that liposomes which are stable in acidic solution, bile, and pancreatin solution would serve effectively as an oral delivery vehicle for inducing mucosal immune responses.

Topics: 1,2-Dipalmitoylphosphatidylcholine; Administration, Oral; Animals; Antibody Formation; Cholesterol; Female; G(M1) Ganglioside; Immunity, Mucosal; Immunization; Immunoglobulin A, Secretory; Immunoglobulin G; Immunoglobulin M; Intestinal Mucosa; Liposomes; Mice; Mice, Inbred BALB C; Phosphatidylcholines; Phosphatidylserines; Phospholipids

In order to evaluate the usefulness of liposomes as oral vaccines, the stability of liposomes and serum IgA antibody response to antigen associated with liposomes after oral administration were examined. Liposomes composed of dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylserine (DPPS), and cholesterol (Chol) (1:1:2, molar ratio), distearoylphosphatidylcholine (DSPC) and Chol (7:2, molar ratio), and DSPC, DPPS, and Chol (7:3:2 or 1:1:2, molar ratio) were stable in acidic solution (pH 2.0), bile, and pancreatin solution, whereas liposomes composed of DPPC and Chol (7:2, molar ratio) and DPPC, DPPS, and Chol (7:3:2, molar ratio) were unstable in pH 2.0 and/or bile solutions. After the oral immunization of antigen (ganglioside GM1)-containing liposomes composed of DPPC, DPPS, and Chol (1:1:2, molar ratio) to mice, the serum IgA antibody responses against ganglioside GM1 were found. Furthermore, when monophosphoryl lipid A was incorporated into liposomes containing ganglioside GM1, further augmentation of IgA responses to ganglioside GM1 was observed. On the other hand, the oral administration with liposomes composed of DPPC, Chol, and ganglioside GM1 (unstable liposomes), ganglioside GM1 mixed with liposomes composed of DPPC, DPPS and Chol, and ganglioside GM1 alone was unable to induce any detectable anti-ganglioside GM1 IgA antibody responses. These results suggest that liposomes which showed the stability to acidic solution, bile, and pancreatin solution would serve effectively as an oral delivery vehicle for inducing mucosal immune responses.

Topics: Administration, Oral; Animals; Antigens; Cholesterol; Drug Stability; G(M1) Ganglioside; Immunoglobulin A; Liposomes; Mice; Mice, Inbred BALB C; Phosphatidylcholines; Phosphatidylserines; Vaccines