Molybdenum Disulfide\nNanosheet-Based Nanocomposite\nfor the Topical Delivery of Umbelliferone: Evaluation of Anti-inflammatory\nand Analgesic Potentials

This study aimed to develop a nanocomposite formulation\ncomprising\numbelliferone (UMB) and molybdenum disulfide (MoS<sub>2</sub>) nanosheets\nas a carrier, termed as the UMB–MoS<sub>2</sub> nanocomposite\nin gel for topical delivery. MoS<sub>2</sub> nanosheets were successfully\nsynthesized via a green-hydrothermal reaction of 10 mg of ammonium\nmolybdate and 10 mg of thiourea in 80 mL of deionized water under\npredetermined conditions. The UMB–MoS<sub>2</sub> nanocomposite\nwas prepared by sonicating UMB and MoS<sub>2</sub> nanosheets (each\nof 1 mg/mL) in dimethylformamide. Scanning electron microscopy revealed\ncrumpled nanosheets with an open-ended structure and a nanocomposite\nas a layered structure. The X-ray diffraction pattern revealed the\namorphous nature of UMB in the UMB–MoS<sub>2</sub> nanocomposite.\nFourier-transform infrared spectra of the UMB–MoS<sub>2</sub> nanocomposite had modified bands of the functional group, which\nconfirmed the formation of the nanocomposite. The size and polydispersity-index\n(435 nm and 0.415, respectively) of the nanocomposite were within\nthe limit for an efficient topical application. Carbopol 934 (2%)\nwas used to prepare the UMB–MoS<sub>2</sub> nanocomposite gel\n(F1) and UMB-Carbopol gel (F2, for comparative evaluation). The pH,\nspreadability, and viscosity of F1 were found to be 5.56, 5.89 g·cm/s,\nand 32.5 Pa-sec, respectively, which were optimal for the topical\napplication of gel-based formulations. In vitro release characteristics\nof both formulations were deemed to be suitable for topical application,\nwhere F1 exhibited a biphasic drug release profile and a superior\nrelease rate of 94.8% compared to 43.5% for F2 at 24 h. In the carrageenan-induced\nrat paw edema model, the animal group treated with F1 demonstrated\nthe lowest increase in paw thickness of 26.6%, which was significantly\nlower as compared to the F2-treated group (52.9%) and the diclofenac\nsodium-treated group (32.2%). Similarly, in the tail immersion method,\nF1 exhibited the highest peak tail withdrawal latency of 10.9 s, significantly\ngreater than F2 (8.9 s) and standard treatment (10 s), indicating\nthe superior analgesic activity of F1. This pioneering work introduces\na novel UMB–MoS<sub>2</sub> nanocomposite with promising anti-inflammatory\nand analgesic potentials, paving the way for further research into\nthe biomedical applications of MoS<sub>2</sub>-based nanocarriers.