It was aim of the study to investigate the in vivo potential of a novel insulin-thiomer complex nanoparticulate delivery system. Insulin loaded nanoparticles were obtained by the formation of hydrogen bonds between poly(vinyl pyrrolidone) (PVP) and poly(acrylic acid)-cysteine (PAA-Cys) or poly(acrylic acid) (PAA), respectively, in the presence of insulin. Dissolution behavior of insulin from tablets as well as nanoparticulate suspensions was evaluated in vitro. Serum insulin concentrations and reduction of blood sugar values were determined after oral administration of nanoparticles formulated as enteric coated tablets and suspensions. Results displayed a low serum insulin concentration and pharmacological efficacy in terms of blood sugar reduction after oral administration of enteric coated tablets. On the contrary, nanoparticulate suspensions led to significant serum insulin concentrations. Furthermore a 2.3-fold improvement of the AUC of insulin could be achieved due to the use of thiolated PAA instead of unmodified PAA. In addition, a blood sugar reduction of 22% was observed. Results demonstrate that this novel complex nanoparticulate formulation is an encouraging new attempt toward the noninvasive delivery of peptide drugs.

No abstract

This study evaluated thiolated poly(acrylic acid) nanoparticles as a valuable tool to protect insulin from degradation by serinproteases of the intestine. Nanaoparticles were characterized concerning particle size, zeta potential, and drug load. Furthermore, in vitro release studies were performed. Within in vitro degradation studies with trypsin, alpha-chymotrypsin, and elastase it could be demonstrated that the obtained nanoparticles are capable of protecting 44.47 +/- 0.89% of the initial insulin amount from tryptic degradation, 21.33 +/- 5.34% from chymotryptic degradation, and 45.01 +/- 1.40% from degradation by elastase compared to insulin solutions.

No abstract

This novel nanoparticulate delivery system seems to be a promising vehicle for the administration of therapeutic proteins, genes and antigens via mucosal membranes.