Liposomal formulations for oral immunotherapy: in-vitro stability in synthetic intestinal media and in-vivo efficacy in the mouse.
The aim of this work was to develop a liposomal formulation which could act as a carrier for allergens during oral desensitization therapy. A model protein, ovalbumin, was associated with negatively charged, multilamellar vesicles of various compositions and their stability in the presence of synthetic intestinal media (bile salt, pancreatic enzymes and their combination) was investigated. Liposomes containing soya phosphatidylcholine as the main lipid, regardless of their cholesterol content (20-40%), were unable to protect ovalbumin against the combined action of pancreatic enzymes and bile salt. In contrast, liposomes prepared from distearoylphosphatidylcholine and cholesterol (6:3.5 molar ratio) were more stable: about 50% of the lipid remained as liposomes after a 4-h incubation at 37 degrees C and intact ovalbumin could be demonstrated therein by immunoblotting. The immunomodulating properties of liposomes were tested by following changes in serum IgE levels (by passive cutaneous anaphylaxis) in Balb/C mice sensitized to ovalbumin, after feeding various preparations. In this model, free ovalbumin was able to provoke a premature fall in IgE levels, and liposomes, whatever their composition, contributed no further effect.
URA CNRS 1218, Université Paris-Sud, Châtenay-Malabry, France.
S
S
Ouadahi
M
M
Paternostre
C
C
André
I
I
Genin
T X
TX
Thao
F
F
Puisieux
J P
JP
Devissaguet
G
G
Barratt
D000276:Adjuvants, Immunologic; D000284:Administration, Oral; D000818:Animals; D003888:Desensitization, Immunologic / Q000379:methods*; D004337:Drug Carriers; D005260:Female; D015151:Immunoblotting; D007073:Immunoglobulin E / Q000096:biosynthesis*; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology; D010713:Phosphatidylcholines / Q000737:chemistry
D000276:Adjuvants, Immunologic; D004337:Drug Carriers; D008081:Liposomes; D010713:Phosphatidylcholines; D007073:Immunoglobulin E; D010047:Ovalbumin; C010942:1,2-distearoyllecithin