Thiomers: development and in vitro evaluation of a peroral microparticulate peptide delivery system.

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.