Molybdenum Disulfide Nanosheet-Based Nanocomposite for the Topical Delivery of Umbelliferone: Evaluation of Anti-inflammatory and Analgesic Potentials

This study aimed to develop a nanocomposite formulation comprising umbelliferone (UMB) and molybdenum disulfide (MoS₂) nanosheets as a carrier, termed as the UMB-MoS₂ nanocomposite in gel for topical delivery. MoS₂ nanosheets were successfully synthesized via a green-hydrothermal reaction of 10 mg of ammonium molybdate and 10 mg of thiourea in 80 mL of deionized water under predetermined conditions. The UMB-MoS₂ nanocomposite was prepared by sonicating UMB and MoS₂ nanosheets (each of 1 mg/mL) in dimethylformamide. Scanning electron microscopy revealed crumpled nanosheets with an open-ended structure and a nanocomposite as a layered structure. The X-ray diffraction pattern revealed the amorphous nature of UMB in the UMB-MoS₂ nanocomposite. Fourier-transform infrared spectra of the UMB-MoS₂ nanocomposite had modified bands of the functional group, which confirmed the formation of the nanocomposite. The size and polydispersity-index (435 nm and 0.415, respectively) of the nanocomposite were within the limit for an efficient topical application. Carbopol 934 (2%) was used to prepare the UMB-MoS₂ nanocomposite gel (F1) and UMB-Carbopol gel (F2, for comparative evaluation). The pH, spreadability, and viscosity of F1 were found to be 5.56, 5.89 g·cm/s, and 32.5 Pa-sec, respectively, which were optimal for the topical application of gel-based formulations. In vitro release characteristics of both formulations were deemed to be suitable for topical application, where F1 exhibited a biphasic drug release profile and a superior release rate of 94.8% compared to 43.5% for F2 at 24 h. In the carrageenan-induced rat paw edema model, the animal group treated with F1 demonstrated the lowest increase in paw thickness of 26.6%, which was significantly lower as compared to the F2-treated group (52.9%) and the diclofenac sodium-treated group (32.2%). Similarly, in the tail immersion method, F1 exhibited the highest peak tail withdrawal latency of 10.9 s, significantly greater than F2 (8.9 s) and standard treatment (10 s), indicating the superior analgesic activity of F1. This pioneering work introduces a novel UMB-MoS₂ nanocomposite with promising anti-inflammatory and analgesic potentials, paving the way for further research into the biomedical applications of MoS₂-based nanocarriers.