Physicochemical, pharmacokinetic and pharmacodynamic analyses of amphiphilic cyclodextrin-based nanoparticles designed to enhance intestinal delivery of insulin.

摘要: Abstract Due to excellent efficacy, low toxicity, and well-defined selectivity, development of new injectable peptides is increasing. However, the translation these drugs into products for effective oral delivery has been restricted due poor bioavailability. Nanoparticle (NP) formulations have potential overcome barriers peptide through protecting payload increasing This study describes rational design, optimization evaluation a cyclodextrin-based NP entrapping insulin glulisine intestinal administration. A cationic amphiphilic cyclodextrin (click propyl-amine (CD)) was selected as primary complexing agent development. Following synthesis, in vitro characterization performed. The NPs exhibited an average size 109 ± 9 nm, polydispersity index (0.272) negative zeta (−25 ± 3 mV), high association efficiency (71.4 ± 3.37%) loading 10.2%. In addition, colloidal stability intestinal-biorelevant media (SIF, supplemented-SIF 1% (w/v) FaSSIF-V2) up 4 h. Proteolysis studies indicated that conferred protection entrapped relative free insulin. vivo rat jejunal instillation demonstrated mediated systemic absorption, accompanied by decrease blood glucose levels. bioavailability instilled (50 IU/kg) from 5.5% compared subcutaneous administration solution (1 IU/kg). pharmacodynamic pharmacokinetic data indicate this formulation may further research dosage form.