Influence of Glutathione on the Bioactivity of Subcutaneously or Orally Administered Insulin to Rats
Zakieh I. Al-Kurdi,
Babur Z. Chowdhry,
Stephen A. Leharne,
Nidal A. Qinna,
Mahmoud M.H. Al-Omari,
Adnan A. Badwan.
The effect of reduced (GSH) and oxidized (GSSG) glutathione on the bioactivity of insulin
was studied. A polyelectrolyte complex (PEC) of insulin with low molecular weight chitosan (13 kDa)
was prepared and characterized. The PEC was then solubilized, in the presence and absence of GSH
and GSSG, in a reverse micelle consisting of oleic acid and two surfactants (PEG-8 caprylic/capric
glycerides and polyglycerol-6-dioleate). The in vitro and in vivo performances of the reverse micelle formulations (RMFs)
were evaluated in rats. At pH 6.5 the association efficiency of the PEC was 76.2%. In vitro insulin release from the RMs
was negligible at pH 1.2 and was markedly increased at pH 6.8. The hypoglycemic activity of insulin in the PEC was reduced
when administered via the subcutaneous route, regardless of the GSH content. On the other hand, the presence of
GSSG significantly enhanced hypoglycemia. When the RMF was administered via the oral route, the presence of GSH
had no effect on the hypoglycemic activity of insulin compared with the GSH free system. However, the presence of
GSSG in the oral preparation increased the hypoglycemic activity of insulin; probably by inhibiting insulin degradation,
thereby prolonging its effect. Thus, incorporation of GSSG in the RMF reduces blood glucose levels in rats and protects
insulin from degradation.
Keywords: Bioactivity, glutathione, low molecular weight chitosan, nanoparticles, oral insulin.
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