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

Abstract

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.

Multiple Roles of Chitosan in Mucosal Drug Delivery: An Updated Review

“…The use of CS in combination with Carbopol 934, poloxamer 407, sodium carboxymethylcellulose and hydroxypropyl methylcellulose, allowed the development of an in situ gel for nose-to-brain delivery of rivastigmine tartrate, which showed a three-times increase of the drug permeation through the nasal membrane and a 3.4-times higher distribution to the brain compared to the simple drug solution [ 158 ]. The use of a mixture of CS, quaternized CS and gelatin allowed the obtaining of a thermosensitive hydrogel with low gelation time, suitable swelling ratio and extended release of insulin up to 24 h, thus demonstrating the potential application of the formulation to improve the absorption of hydrophilic macromolecular drugs through the nasal route [ 159 ].…”

Biomaterials and Extracellular Vesicle Delivery: Current Status, Applications and Challenges

“…Chitosan is a cationic polysaccharide derived from chitin and is made up of diglucose amine and N-acetyl glucose amine groups [ 81 , 82 , 83 ]. Antibiotics [ 81 , 83 ], antivirals [ 84 ], and immunosuppressants [ 85 ] have been delivered using chitosan.…”

“…Antibiotics [ 81 , 83 ], antivirals [ 84 ], and immunosuppressants [ 85 ] have been delivered using chitosan. Additionally, chitosan has been utilized to deliver insulin [ 82 ] and genetic material [ 86 , 87 , 88 ].…”

A Comprehensive Review of the Evolution of Insulin Development and Its Delivery Method

“…The authors concluded that gel: Ch-HTCC (1:6) consisting of 2 wt% chitosan, 1 wt% HTCC, and 0.5 wt% Gel provides the best results with a prolonged release of insulin rate. This formulation could be used in the future for delivery of insulin in a controlled release and for a prolonged time [ 85 ]. In Vivo …”