Thiomers in noninvasive polypeptide delivery: in vitro and in vivo characterization of a polycarbophil-cysteine/glutathione gel formulation for human growth hormone.
This study was aimed at investigating the potential of a new polycarbophil-cysteine (PCP-Cys)/glutathione (GSH) gel formulation to enhance the permeation of the model drug human growth hormone (hGH) across nasal mucosa in vitro and in vivo. The aqueous nasal gel contained PCP-Cys, GSH, and hGH in a final concentration of 0.3%, 0.5%, and 0.6% (m/v), respectively. In vitro permeation studies were performed in Ussing chambers on freshly excised bovine nasal mucosa using fluorescence-labeled dextran (molecular mass: 4.3 kDa; FD-4) and hGH (FITC-hGH). The release profile of FITC-hGH from the gel formulation and an unmodified PCP control formulation was determined. Furthermore, in vivo studies in rats were performed comparing the PCP-Cys/GSH/hGH gel with PCP/hGH control gel and physiological saline. The permeation of FD-4 and FITC-hGH across the nasal mucosa was improved two-fold and three-fold, respectively, in the presence of PCP-Cys/GSH. The PCP-Cys/GSH/hGH gel and the PCP/hGH control gel showed the same biphasic and matrix-controlled drug release. The nasal administration of the PCP-Cys/GSH/hGH gel formulation to rats resulted in a significantly increased and prolonged hGH plasma concentration-time profile versus unmodified PCP gel and physiological saline. According to these results, PCP-Cys gels might represent a promising new strategy for systemic nasal polypeptide delivery.
Leitner
Verena M
VM
Institute of Pharmaceutical Technology and Biopharmaceutics, Center of Pharmacy, University of Vienna, Althanstr. 14, A-1090 Vienna, Austria.
Guggi
Davide
D
Bernkop-Schnürch
Andreas
A
D000180:Acrylic Resins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D002417:Cattle; D002626:Chemistry, Pharmaceutical; D003545:Cysteine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D005782:Gels; D005978:Glutathione / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019382:Human Growth Hormone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D008297:Male; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000008:administration & dosage / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar
D000180:Acrylic Resins; D005782:Gels; D010455:Peptides; D019382:Human Growth Hormone; C030312:calcium polycarbophil; D005978:Glutathione; D003545:Cysteine