Pharmacokinetics and Brain Tumor Delivery Studies of Thymoquinone-Encapsulated Eudragit L100-Coated Solid-Lipid Nanoparticles

Brain tumor is one of the deadliest types of cancer in the world. The basic necessity of brain tumor-targeted therapy is to reach and accumulate the required quantity in the tumor microenvironment while maintaining therapeutic efficacy. In this regard, the current study sought to create thymoquinone-encapsulated Eudragit L100-coated solid lipid nanoparticles (TQ-encapsulated E-SLNs) for the transport of loaded thymoquinone (TQ) to the brain. TQ-encapsulated E-SLNs were formulated using the oil-in-water microemulsion process, and their physicochemical properties were investigated. TQ encapsulation, loading capacity, and release behavior of E-SLNs were also investigated. In vivo biodistribution studies were conducted to assess TQ delivery and accumulation in several organs of female Wistar rats. The TQ-encapsulated E-SLNs were mostly spherical with a crystalline structure and extremely stable in the physiological buffer system. The highest content of TQ was released in pH 5.5 (78.215 ± 0.749%) at 22 h. The pharmacokinetics and biodistribution investigations revealed that released TQ from TQ-encapsulated E-SLNs after 48 h of administration accumulated 16.5 ± 1.5% in brain, 21.167 ± 1.041% in kidneys, 12.125 ± 0.781% in heart, 16.375 ± 1.317% in liver, 13.5 ± 1.8% in lungs, and 17.15 ± 1.5%. Later, molecular modeling studies revealed that TQ had a greater binding energy of -7.8 kcal/mol to EGFR. Thymoquinone binding energy was very close to the reference drug Temozolomide. Molecular dynamics simulation studies showed that the TQ-EGFR docked complex was extremely stable up to 100 ns. The findings showed that the fabricated TQ-encapsulated E-SLNs remained unchanging in circulation for up to five days. Therefore, E-SLNs fabrications show promise as a method for targeting brain malignancies across the BBB.