Novel Insulin Thiomer Nanoparticles: In Vivo Evaluation of an Oral Drug Delivery System

Abstract

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.

The use of chitosan-6-mercaptonicotinic acid nanoparticles for oral peptide drug delivery

“…Indeed the AUC of insulin for chitoasan-TBA was 2.95-fold higher compared to unmodified chitosan (Krauland et al, 2004). Poly(vinyl pyrrolidone) combined with poly(acrylic acid)-cysteine particles showed a 2.3-fold improvement of the AUC of insulin compared to the non-thiolated formulation (Deutel et al, 2008). Furthermore, the pharmacological efficacy of trimethyl chitosan-cysteine in decreasing the blood glucose level was 1.1-fold higher compared to unmofidied chitosan and its increased insulin transport through rat intestine compared to unmodified chitosan was 1.7-2.6-fold improved (Yin et al, 2009).…”

Development and in vivo evaluation of a new oral nanoparticulate dosage form for leuprolide based on polyacrylic acid

“…Therefore, PVP (10,11,12) exhibiting a carboxylic moiety, and Pluronic F68 with polyether structure were chosen. In order to decide between the two polymers and to determine optimal ratios, titration experiments at varying ratios were performed and monitored by absorbance measurement at 400 nm.…”

Progress in Nanoparticulate Systems for Peptide, Proteins and Nucleic Acid Drug Delivery

“…Polymers with thiol groups were obtained by reacting activated (with 1-methyl-3-(3-diethylaminopropyl) carbodiimide hydrochloride) carboxylic groups of polymers containing cysteine (see Scheme 6) [11,75,76].…”

“…Formulation of thiolated poly(acrylic acid), unmodified poly(acrylic acid), poly(N-vinylpyrrolidone) and insulin into nanoparticle suspension or tablets made of nanoparticles were found to be suitable for oral insulin administration [11].…”