Insulin Containing Nanocomplexes Formed by Self-Assembly from Biodegradable Amine-Modified Poly(Vinyl Alcohol)-Graft-Poly(l-Lactide): Bioavailability and Nasal Tolerability in Rats
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- Simon, M., Wittmar, M., Kissel, T. et al. Pharm Res (2005) 22: 1879. doi:10.1007/s11095-005-7676-z
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The bioavailability and local tolerability of insulin containing nanocomplexes from amine-modified poly(vinyl alcohol)-graft-poly(l-lactide) were studied in rats. Histology of the nasal epithelium was studied to document integrity of the mucosa.
Nanocomplexes (NC) were prepared by spontaneous self-assembly of insulin and the water-soluble amphiphilic polymer. Changes in blood glucose and insulin blood concentration were monitored in anesthetized rats using a glucose meter and enzyme-linked immunosorbent assay, respectively. Histological sections of the nasal cavity were examined after H&E staining by light microscopy.
NC reduced blood glucose level in fasted healthy rats by 20% after 50–80 min and in streptozotocin induced diabetic rats by 30% within 75–95 min compared to basal levels. In both animal models significant concentrations of human insulin were detected, with relative bioavailabilities Frel of 2.8 up to 8.3%. The more hydrophobic, lactic acid grafted polyester were more effective at a threefold higher polymer concentration, increasing the relative bioavailability Frel of a 5 IU/kg dose from 2.8 to 5.7%. Histological examination of the nasal mucosa after 4 h showed no signs of toxicity at the site of nasal administration.
These results demonstrate that the NC significantly enhanced insulin absorption, suggesting that amphiphilic biodegradable comb-polymers offer a promising approach for nasal peptide delivery.