A novel insulin oral delivery system assisted by cationic β‐cyclodextrin polymers

This work describes a new oral pharmaceutical formulation of insulin that is complexed with cationic β‐cyclodextrin polymers (CPβCDs), and then encapsulated into alginate/chitosan microspheres, which are prepared by ionotropic pregelation/polyelectrolyte method. CPβCDs were synthesized through a one‐step polymerization of β‐cyclodextrin (βCD), epichlorohydrin, and choline chloride. CPβCDs have enhanced ability to complex with insulin due to the assistance of their polymeric chains, as well as the electrostatic interactions between insulin (negatively charged while pH>5.3) and quaternary ammonium groups of CPβCDs. The noncovalent inclusion complex formed between CPβCDs and insulin was analyzed by Fourier transform infrared and fluorescence emission spectra. With the increase of zeta potential of CPβCDs from 1.8 to 14.2 mV, the insulin association efficiency (AE) of current system was increased from 55.2 to 71.8%, whereas the AE of insulin‐loaded microspheres at the same condition was only 50.7%. The cumulative insulin release in simulated intestinal fluid was also higher than that of the insulin‐loaded microspheres and βCD‐insulin encapsulated microspheres.