Hydrophobic ion pairing of an insulin-sodium deoxycholate complex for oral delivery of insulin

Abstract

Insulin was complexed with sodium deoxycholate to form an insulin-sodium deoxycholate complex (Ins-SD-Comp) using an hydrophobic ion pairing method in aqueous phase to enhance the liposolubility of insulin. In order to obtain the maximal complexation efficiency, the molar ratio of sodium deoxycholate to insulin was found. The zeta potential method was used to confirm the optimal ratio for formation of Ins-SD-Comp. The structural characteristics of Ins-SD-Comp were assessed using the Fourier transform infrared method. The apparent partition coefficient of insulin increased upon the formation of Ins-SD-Comp. Based on the preliminary study, Ins-SD-Comp was encapsulated into poly(lactide-co-glycolide) (PLGA) nanoparticles using an emulsion solvent diffusion method. The maximal encapsulation efficiency of Ins-SD-Comp into PLGA nanoparticles was 93.6% ± 2.81%, drug loading was about 4.8% ± 0.32%, and the mean diameter of the nanoparticles was 278 ± 13 nm. Biological activity and in vivo results revealed that the bioactivity of insulin was not destroyed during the preparation process. Ins-SD-Comp-loaded PLGA nanoparticles have the potential to reduce serum glucose levels and increase the oral bioavailability of insulin.

A novel approach for antibody nanocarriers development through hydrophobic ion-pairing complexation

“…Moreover, there are also possibility of strong hydrogen bonding between TA and Fab as it possesses both hydrogen acceptor and donor groups. Other researchers have reported presence of ionic interaction between protein with SDS and bile acids (Yang et al, 2009; Sun et al, 2011). However, in this case, with SDS and TA as ion-pairing agent the complexation may preferentially involve hydrophobic interactions rather than ionic interactions.…”

“…The observed peaks are consistent with previously published results. The ionic interactions can be interpreted in terms of attenuation in observed IR peaks for sulphate group or shift in the peaks (Sun et al, 2011). Due to such interactions between amino and sulphate groups, a peak for sulphate group in the IR region has been diminished.…”

“…The percentage binding efficiency was expressed as the percentage Fab difference between the initial amount of Fab and the free amount in the supernatant relative to the initial amount of Fab added for the complex preparation. Percentage binding efficiency of Fab was calculated according to Equation (1) (Sun et al, 2011). …”

“…Moreover, the selection of ion-pairing agents also depends on properties of therapeutic proteins being complexed such as isoelectric point, molecular weight and number of charges in both protein and ion-pairing agent. Till now, this approach has been employed for the delivery of various peptides and proteins such as insulin, melittin, leuprolide, bovine serum albumin (BSA) and lysozyme (Choi and Park, 2000; Yoo et al, 2001; Shi et al, 2008; Yang et al, 2009; Sun et al, 2010; Gaudana et al, 2011a; Sun et al, 2011). Sodium dodecyl sulphate (SDS) is the most commonly employed ion-pairing agent in HIP complexation (Shi et al, 2008; Yang et al, 2009).…”

“…Sodium dodecyl sulphate (SDS) is the most commonly employed ion-pairing agent in HIP complexation (Shi et al, 2008; Yang et al, 2009). In addition, there are also few reports regarding use of dextran sulphate and bile acids such as cholic acid and deoxycholic acid (Dalwadi and Sunderland, 2009; Yang et al, 2009; Sun et al, 2011; Gaudana et al, 2011a). To the best of our knowledge, application of HIP complexation in delivery of monoclonal antibody-based protein therapeutics has never been reported.…”