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Comparative Study
. 2015 Mar 30;13(4):1765-84.
doi: 10.3390/md13041765.

Low molecular weight chitosan-insulin polyelectrolyte complex: characterization and stability studies

Zakieh I Al-Kurdi  1   2 , Babur Z Chowdhry  3 , Stephen A Leharne  4 , Mahmoud M H Al Omari  5 , Adnan A Badwan  6
Affiliations
Comparative Study

Low molecular weight chitosan-insulin polyelectrolyte complex: characterization and stability studies

Zakieh I Al-Kurdi et al. Mar Drugs. .

Abstract

The aim of the work reported herein was to investigate the effect of various low molecular weight chitosans (LMWCs) on the stability of insulin using USP HPLC methods. Insulin was found to be stable in a polyelectrolyte complex (PEC) consisting of insulin and LMWC in the presence of a Tris-buffer at pH 6.5. In the presence of LMWC, the stability of insulin increased with decreasing molecular weight of LMWC; 13 kDa LMWC was the most efficient molecular weight for enhancing the physical and chemical stability of insulin. Solubilization of insulin-LMWC polyelectrolyte complex (I-LMWC PEC) in a reverse micelle (RM) system, administered to diabetic rats, results in an oral delivery system for insulin with acceptable bioactivity.

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Figures

Figure 1
Figure 1
Representative HPLC chromatograms for (A) insulin assay (1.5 mg/mL) and (B) high molecular weight proteins (HMWPs) limit test (4.0 mg/mL).
Figure 2
Figure 2
Stability of insulin in the presence of (A) different LMWCs (1.5 mg/mL) and (B) different concentrations of 13 kDa LMWC at 50 °C. Co is the initial insulin concentration and Ct is the insulin concentration at different periods of incubation time. The values of Ln (Ct/Co) are the mean of 3 replicates for each experiment (RSDs < 5%).
Figure 3
Figure 3
Effect of 13 kDa LMWC concentration on (A) the particle size of major peaks at 100–250 nm and (B) the zeta potential of the insulin–LMWC polyelectrolyte (I-LMWC PEC). The number of replicates is 6 and 3, respectively.
Figure 4
Figure 4
A cumulative release of insulin from insulin–LMWC reverse micelles (I-LMWC RMs) using 13 kDa LMWC.
Figure 5
Figure 5
Blood glucose levels versus time profile after a single oral administration of 50 IU/kg insulin-LMWC reverse micelle (I-LMWC RM) and a subcutaneous administration (SC) of 2 IU/kg insulin to STZ-diabetic rats The results are expressed as mean ± SD (n = 10 for each group).
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