Gliadin nanoparticles as carriers for the oral administration of lipophilic drugs. Relationships between bioadhesion and pharmacokinetics.
OBJECTIVE
The aim of this work was to evaluate the bioadhesive properties of non-hardened gliadin nanoparticles (NPs) and cross-linked gliadin nanoparticles (CL-NP) in the carbazole pharmacokinetic parameters obtained after the oral administration of these carriers.


METHODS
A deconvolution model was used to estimate the carbazole absorption when loaded in the different gliadin nanoparticles. In addition, the elimination rates of both adhered and non-adhered nanoparticulate fractions within the stomach were estimated.


RESULTS
Nanoparticles dramatically increased the carbazole oral bioavailability up to 49% and provided sustained release properties related to a decrease of the carbazole plasma elimination rate. The carbazole release rates from nanoparticles (NP and CL-NP), calculated by deconvolution, were found to be of the same order as the elimination rates of the adhered fractions of nanoparticles in the stomach mucosa. In addition, good correlation was found between the carbazole plasmatic levels, during the period of time in which the absorption process prevails, and the amount of adhered carriers to the stomach mucosa.


CONCLUSIONS
Gliadin nanoparticles significantly increased the carbazole bioavailability, providing sustained plasma concentrations of this lipophilic molecule. These pharmacokinetic modifications were directly related to the bioadhesive capacity of these carriers with the stomach mucosa.
Arangoa
M A
MA
Centro Galénico, Departamento de Farmacia y Tecnología Farmacéutica, Universidad de Navarra, Pamplona, Spain.
Campanero
M A
MA
Renedo
M J
MJ
Ponchel
G
G
Irache
J M
JM
D000284:Administration, Oral; D000465:Algorithms; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002227:Carbazoles / Q000008:administration & dosage / Q000493:pharmacokinetics; D002448:Cell Adhesion; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers; D005903:Gliadin / Q000737:chemistry*; D008297:Male; D008863:Microspheres; D036103:Nanotechnology; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry; D010599:Pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D014014:Tissue Adhesives
D002227:Carbazoles; D004337:Drug Carriers; D004364:Pharmaceutical Preparations; D014014:Tissue Adhesives; C041514:carbazole; D005903:Gliadin