Thermosensitive chitosan hydrogel loaded cetuximab: a novel approach for parenteral controlled delivery.

Objective: The controlled release method improves the stability of cetuximab (CTX), which is typically impacted by the environmental variables present in regular formulations.

Significant: It is possible to preserve the effectiveness of CTX by encapsulating it in a chitosan hydrogel to reach the target site via direct injection easily.

Method: CTX was loaded into the thermosensitive polymer-based hydrogel, namely chitosan (CH) with the aid of a crosslinking β-glycerophosphate (β-GP) alone or in combination with Pluronic F127 ($\text{Pl F}127$). The formulated hydrogels were subjected to different types of characterizations, such as stability and rheological studies. Furthermore, they were tested for their antiproliferative activities against HEPG2 (hepatic cancer cell lines).

Results: Hydrogels had a homogeneous preparation, were transparent, and showed no signs of aggregation. Moreover, CH/β-GP gel type recorded a lower viscosity in comparison to the other hydrogel type $\text{CH}/\beta -\text{GP}/\text{Pl F}127$ system of (110.3 ± 5.2, and 148.4 ± 4.4 Cp, respectively). The conducted pharmacokinetic studies demonstrated a continued increase in rabbits' plasma throughout the first four days (T_max) with C_max of 3.663 μg/mL which also showed a decline below the detected limit after 15 days. Nevertheless, the formulated CH-based hydrogel showed a sustained release with a longer value of MRT of more than 9 days with an estimated AUC_0-t of 41.917 μg/L/day.

Conclusion: The medicated CH/β-GP hydrogel formula demonstrated superior targeting-controlled efficiency compared to free CTX.