<I>N</I>-Octyl-<I>N</I>-Arginine Chitosan Micelles as an Oral Delivery System of Insulin

Abstract

N-octyl-N-Arginine chitosan (OACS) was synthesized in an attempt to combine the permeation enhancing effects of arginine-rich peptides and the drug loading capacity of the amphipathic polymers for insulin oral delivery. OACS self-assembled micelles of insulin were prepared by the conventional stirring technique, which were characterized by Dynamic light scattering, transmission electron microscopy and differential scanning calorimetry. Molecular docking by Discovery studio software confirmed that the interactions between OACS and insulin were mostly electrostatic in nature. In vitro, the result of the degradation experiment by enzyme showed that the OACS has a relative protective effect for insulin from proteolyses. Compared to the insulin solution, OACS micelles increased the Caco-2 cell's internalization by up to 22.3 folds. In vivo, the pharmacological activity PA% of series OACS-insulin micelles ranged from 7.7%-16.8%. Meanwhile by increasing arginine degree of the substitution both the uptake in Caco-2 cells and the hypoglycemic effect in diabetic rats were enhanced. Therefore, it is concluded that using arginine polymeric micelles for the enhancement of oral insulin delivery is a promising approach for the oral peptide delivery.

The studies of N-Octyl-N-Arginine-Chitosan coated liposome as an oral delivery system of Cyclosporine A

“…Furthermore, OACS's hydrophilic arginine groups with positive charge can be tightly absorbed with the negatively charged liposomes. Therefore, arginine's guanidino group could mimic arginine‐rich cell‐penetrating peptides in forming rich cationic layers on the surface of liposomes, providing an advantage in cell penetration and absorption enhancement as we have previously reported [15–18]. The results of enhancement of bioavailability of OACS‐CL and Tianke also confirmed the absorption promoting function of OACS.…”

“…OACS was synthesized in our laboratory as previously described [15]. Chemical structure of the obtained polymer was characterized by Fourier Transform Infrared spectra (FT‐IR) and Nuclear Magnetic Resonance Hydrogen ( 1 H‐NMR) and its substitution degree was calculated through element analysis [16]…”

“…N‐Octyl‐N‐Arginine‐Chitosan (OACS) was synthesized by introducing hydrophilic arginine groups and hydrophobic octyl groups to the amino‐group on chitosan's side chain [15]. It is a chitosan derivative with the permeation‐enhancing effects of arginine‐rich peptides and the drug loading (DL) capacity of the amphipathic polymers [16]. OACS also has the same excellent biocompatibility with chitosan [15,16].…”

In vitroevaluation of antioxidant and neuroprotective effects of curcumin loaded in Pluronic micelles

“…The sample was agitated (50 r/min) and the temperature was constantly maintained at 37 C throughout the study. At predetermined time intervals (2,4,6,8,24, 48 h), samples were withdrawn from the medium outside the dialysis bag and the concentration of the released curcumin was determined by UV-Vis spectrophotometry as described above.…”

“…[3] Insulin has been incorporated in arginine polymeric micelles, which provided protective effect against enzymatic degradation of insulin and hypoglycemic effect in diabetic rats. [4] Curcumin is a polyphenolic substance that is attractive due to various activities like antioxidant, anti-inflammatory, anticancer ones, etc. However, the administration of curcumin is associated with very low bioavailability.…”