title: Thiomers: development and in vitro evaluation of a peroral microparticulate peptide delivery system.
abstract: The aim of this study was to develop a peroral mucoadhesive microparticulate delivery system for peptide drugs. Microparticles containing either the mucoadhesive polymer poly(acrylic acid)-cysteine (PAA-Cys) or unmodified PAA, 15% insulin used as model peptide drug and 0, 30, 50 and 70% Eudragit RS (MP-RS0, MP-RS30, MP-RS50 and MP-RS70) were prepared by the emulsification solvent evaporation technique. Particle size distribution, release of incorporated insulin, mucoadhesive and swelling properties were examined. During preparation inter- and intramolecular cross-linking occurred, which could be quantified by the amount of disulfide bonds within the resulting particles; this was determined to be 69.2% of the total amount of thiol groups. This cross-linking led to a higher stability of the particles. Microparticles were spherical displaying a rough surface. The particle diameter was in the range of 1-110 microm in the following rank order beginning with the largest: MP-RS30>MP-RS50>MP-RS70=MP-RS0. The higher the ratio of Eudragit RS in the microparticles, the more prolonged was the release of insulin. In the case of MP-RS70, a sustained release over a time period of at least 60 min was achieved. Mucoadhesive properties and the capacity of water uptake followed the rank order: MP-RS0>MP-RS30>MP-RS50>MP-RS70. Compared to particles comprising unmodified PAA, the mucoadhesive properties of the thiolated microparticulate systems were up to 14-fold improved. According to these results PAA-Cys-Eudragit RS microparticles might be a promising tool for the peroral administration of peptide drugs.
authors.affiliation: Institute of Pharmaceutical Technology and Biopharmaceutics, Center of Pharmacy, University of Vienna, Vienna, Austria.
authors.forename: Alexander H
authors.initials: AH
authors.lastname: Krauland
authors.forename: Andreas
authors.initials: A
authors.lastname: Bernkop-Schnürch
mesh_terms: D000180:Acrylic Resins / Q000008:administration & dosage / Q000493:pharmacokinetics; D000818:Animals; D002417:Cattle; D003545:Cysteine / Q000008:administration & dosage / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism; D008863:Microspheres; D010455:Peptides / Q000008:administration & dosage*; D013438:Sulfhydryl Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013552:Swine
chemical_list: D000180:Acrylic Resins; D010455:Peptides; D013438:Sulfhydryl Compounds; C050528:Eudragit RS; C006903:carbopol 940; D003545:Cysteine