Synthesis and characterization of thermosensitive hydrogel based on quaternized chitosan for intranasal delivery of insulin.

Nasal administration is a form of systemic administration in which drugs are insufflated through the nasal cavity. Steroids, nicotine replacement, anti-migraine drugs, and peptide drugs are examples of the available systematically active drugs as nasal sprays. For diabetic patients who need to use insulin daily, the nasal pathway can be used as an alternative to subcutaneous injection. In this regard, intranasal insulin delivery as a user-friendly and systemic administration has recently attracted more attention. In this study, a novel formulation consists of chitosan, chitosan quaternary ammonium salt (HTCC) and gelatin was proposed and examined as a feasible carrier for intranasal insulin administration. Firstly, the optimization of the chitosan-HTCC hydrogel combination has done. Afterward, gelatin with various amounts blended with the chitosan-HTCC optimized samples. In the next step, swelling rate, gelation time, degradation, adhesion, and other mechanical, chemical and biological properties of the hydrogels were studied. Finally, insulin in clinical formulation and dosage was blended with optimized thermosensitive hydrogel and the release procedure of insulin was studied with electrochemiluminescence (ECL) technique. The optimal formulation (consisted of 2 wt % chitosan, 1 wt % HTCC and 0.5 wt % gelatin) showed low gelation time, uniform pore structure and the desirable swelling rate which were resulted in the adequate encapsulation and prolonged release of insulin in 24 hours. The optimal samples released 65 % of the total amount of insulin in the first 24 hours which is favorable for this study. This article is protected by copyright. All rights reserved.