Development and characterization of hydrogel-based insulin delivery systems for topical use

INTRODUCTION. Preclinical and clinical studies indicate that topical insulin may accelerate wound healing by promoting cell proliferation, collagen synthesis, re-epithelialisation, and angiogenesis while reducing inflammation and oxidative stress. The development of effective insulin-containing hydrogels remains challenging. This study aimed to develop and evaluate insulin-loaded hydrogels for potential application in skin regeneration and repair. Two carriers were investigated: sodium alginate and a sodium alginate–hyaluronic acid combination.

MATERIALS AND METHODS. Hydrogels containing 1 mg/g insulin (Insulatard® Penfill®) were prepared according to the 12th edition of the Polish Pharmacopoeia using sodium alginate (F1) or sodium alginate with hyaluronic acid (F2). In vitro insulin release was evaluated using a paddle apparatus with Enhancer Cell™ chambers and a Strat-M® membrane. Rheological properties were determined using an RM 200 Touch rotational rheometer (Lamy Rheology Instruments). We assessed the spreadability of insulin-containing hydrogels using the two-glass method at loads of 20–700 g by measuring the radius of a 300 mg sample after 30 seconds. The pH of the hydrogels was determined using the potentiometric method with a SevenCompact™ S210 pH meter. The hydrogels remained stable during 4 weeks’ storage at 25±1°C and 5±3°C, in accordance with the ICH Q5C guidelines.

RESULTS. The formulations developed were characterised by a prolonged insulin release profile. The bioavailability of insulin from the hydrogels was 60.11% over 7 hours (F1) and 55.88% over 8 hours (F2). Rheological analysis showed that the resulting preparations are non-Newtonian, shear-thinning fluids with thixotropic properties. The best fit was obtained for the Herschel–Bulkley model (a pseudoplastic fluid with a yield point). Hydrogels based on sodium alginate and sodium alginate, and hyaluronic acid containing insulin are characterised by comparable spreadability and a pH value within the optimal range for the skin (pH = 7.18 and pH = 7.42, respectively).

CONCLUSIONS. The pre-formulation studies carried out indicate that the hydrogel matrices developed represent a promising system for the local delivery of insulin; however, they require further investigation, including an assessment of their cytotoxicity and biocompatibility.

This research was financed by the Medical University of Silesia in Katowice: No. BNW-1-064/K/5/F.