Effects of N‐trimethyl chitosan chloride as an absorption enhancer on properties of insulin liquid suppository in vitro and in vivo

Abstract

AbstractN‐trimethyl chitosan chloride (TMC), with degree of quaternization (DQ) of 42.77% (TMC40) and 63.03% (TMC60), respectively, were synthesized and used as absorption enhancers in an insulin rectal liquid suppository from poloxamers. The effects of the TMCs on the liquid suppository were investigated. Compared with sodium salicylate (10%), which increased the gelation temperature and decreased the gel strength and bioadhensive force of the liquid suppository, both TMCs increased the three indices due to hydrogen bonding between the amino groups of TMCs and hydroxyl groups of poloxamers. The higher the concentration of TMCs was, the higher the three indices were. At the same concentration, the enhancing effect of TMC60 was higher than that of TMC40. Compared with those of 10% sodium salicylate, the enhancing effects of TMC40 with concentrations of 0.05% and 0.10% and TMC60 with concentration of 0.05% were weaker, while the other testing concentrations all showed better absorption enhancing ability with lower plasma glucose levels, AUC0–4 h (the area below basal glucose level) and Cnadir (the plasma glucose levels at the nadir). Histological assessment was performed by observing irritation of the liquid suppository on the rectal tissues and observation rate of three types of gland changes in the rectal epithelium. Compared with the control (75.48 ± 16.76), TMC40 and TMC60 exhibited little change in observation rates of normal gland (72.10 ± 10.24 and 71.93 ± 9.88, respectively), while sodium salicylate showed significant lower observation rates of normal gland (51.28 ± 13.44). The insulin rectal liquid suppository with TMCs is more effective and safer than that with sodium salicylate. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 99: 1140–1146, 2006