Biomaterial Group, Faculty of Biomedical Engineering (Center of Excellence), Amirkabir University of Technology, Tehran, Iran.
Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.
Biotechnol Appl Biochem. 2021 Apr;68(2):247-256. doi: 10.1002/bab.1917. Epub 2020 May 20.
Nasal administration is a form of systemic administration in which drugs are insufflated through the nasal cavity. Steroids, nicotine replacement, antimigraine 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 (Gel) was proposed and examined as a feasible carrier for intranasal insulin administration. First, the optimization of the chitosan-HTCC hydrogel combination has done. Afterward, Gel 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 technique. The optimal formulation (consisted of 2 wt% chitosan, 1 wt% HTCC, and 0.5 wt% Gel) 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 H. The optimal samples released 65% of the total amount of insulin in the first 24 H, which is favorable for this study.
鼻腔给药是一种全身给药的形式，药物通过鼻腔吸入。目前可用的具有全身活性的鼻腔喷雾剂药物包括类固醇、尼古丁替代物、偏头痛治疗药物和肽类药物。对于需要每天使用胰岛素的糖尿病患者，鼻腔途径可以替代皮下注射。在这方面，作为一种用户友好型和全身给药的鼻内胰岛素输送最近引起了更多的关注。在这项研究中，提出并研究了一种由壳聚糖、壳聚糖季铵盐（HTCC）和明胶（Gel）组成的新型制剂，作为鼻内胰岛素给药的可行载体。首先，对壳聚糖-HTCC 水凝胶组合进行了优化。然后，将不同量的 Gel 与优化后的壳聚糖-HTCC 样品混合。在下一步中，研究了水凝胶的溶胀率、凝胶时间、降解、粘附和其他机械、化学和生物学特性。最后，将临床制剂和剂量的胰岛素与优化的温敏水凝胶混合，并用电化学发光技术研究胰岛素的释放过程。最佳配方（由 2wt%壳聚糖、1wt%HTCC 和 0.5wt%Gel 组成）表现出低凝胶时间、均匀的孔结构和理想的溶胀率，这导致胰岛素在 24 小时内得到充分包封和延长释放。最佳样品在前 24 小时内释放了 65%的总胰岛素量，这对本研究很有利。
