Carboxymethyl high amylose starch for F4 fimbriae gastro-resistant oral formulation.
The carboxymethyl high amylose starch (CM-HAS) was proposed as excipient able to protect F4 fimbriae oral vaccine against gastric acidity and pepsin, allowing its subsequent liberation in the intestinal fluid. Thus, F4 fimbriae formulated with CM-HAS as tablets displayed a markedly higher stability after 2h of incubation in simulated gastric fluid (containing pepsin) than the free, non-protected F4 fimbriae, which, in these conditions, were almost completely digested after 120 min. In the presence of pancreatin (with alpha-amylase, lipase and proteolytic activities) in simulated intestinal conditions, the F4 fimbriae were liberated from CM-HAS tablets over a period of up to 5 h. The presence of pancreatin in intestinal medium did not affect the structural stability of the F4 fimbriae major subunits. Thus, F4 fimbriae formulated with CM-HAS would retain their receptor binding activity essential for the induction of an intestinal mucosal immune response.
Calinescu
Carmen
C
Department of Chemistry and Centre BioMed, Université du Québec à Montréal, C.P. 8888, Succ. A, Montréal (Québec), Canada H3C 3P8.
Nadeau
Eric
E
Mulhbacher
Jérome
J
Fairbrother
John Morris
JM
Mateescu
Mircea-Alexandru
MA
D000284:Administration, Oral; D000688:Amylose / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism*; D001428:Bacterial Vaccines; D004355:Drug Stability; D005079:Excipients / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D010861:Fimbriae, Bacterial / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D005750:Gastric Juice / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007419:Intestinal Secretions / Q000378:metabolism; D010194:Pancreatin / Q000378:metabolism; D010434:Pepsin A / Q000378:metabolism; D013607:Tablets; D014867:Water / Q000737:chemistry
D001428:Bacterial Vaccines; D005079:Excipients; D013607:Tablets; D014867:Water; D010194:Pancreatin; D000688:Amylose; D010434:Pepsin A