g(m1)-ganglioside and dipalmitoylphosphatidylserine

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

Unilamellar liposomes made up of DPPC-DPPS-Chol (7:4:7 molar ratio) and ganglioside GM1 8% mol were used to deliver cytidine-5I-diphosphate choline (CDP-choline) to the brain. The liposomal suspension consisted of unilamellar vesicles with a mean size of 50 nm and a very narrow size distribution. The therapeutic effectiveness of CDP-choline-loaded liposomes was investigated by an in vivo model of cerebral ischemia on Wistar rats (320-350 g). The animals were made ischemic to different extents (5, 15 and 30 min) by bilateral clamping of the common carotid arteries. The effect of free and liposomally encapsulated CDP-choline on the survival rate of post-ischemic reperfused rats was evaluated. The liposome formulation was much more active against ischemic injury than the free CDP-choline, ensuring a noticeable improvement of the survival rate with regards to the free drug ranging from 45% to 100% as a function of the duration of the ischemic event.

Topics: 1,2-Dipalmitoylphosphatidylcholine; Animals; Brain Ischemia; Carotid Artery, Common; Cholesterol; Constriction; Cytidine Diphosphate Choline; G(M1) Ganglioside; Liposomes; Male; Phosphatidylserines; Rats; Rats, Wistar; Survival Rate

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