• NLT-SPLs were optimized using a Box-Behnken design. • Optimized NLT-SPLs enhanced oral bioavailability 2.5-fold. • The nanoformulation prolonged Tmax and sustained drug levels. • NLT-SPLs displayed superior cytotoxicity in AML cell lines. • SPL formulation significantly improved Caco-2 permeability. Nilotinib (NLT) has low aqueous solubility and high lipophilicity resulting in lower oral bioavailability and thus reduced therapeutic effectiveness. Nanospanlastics, a flexible nanovesicular drug carrier, represent a potential solution to the above-mentioned absorption problem. To design and optimize NLT-loaded spanlastics (NLT-SPL) to improve NLT oral bioavailability and drug efficacy. NLT-SPL vesicles were prepared by thin-film hydration and refined using Design-Expert design-of-experiments methodology. Certain parameters of the formulations (vesicle size, polydispersity index, zeta potential, and encapsulation efficiency) were optimized to secure an optimal formulation. The optimized formula was characterized for deformability, stability, and in vitro drug release. Performance was evaluated by pharmacokinetic studies (oral administration) and in vitro assays (cytotoxicity on HL-60 and HEL leukemia cells, Caco-2 monolayer permeability). An optimized NLT-SPL (75 mg Phospholipon 90 G, 20 mg Tween 80 and 65 mg Span 60) was evaluated showing nanoscopic size, increased PDI and zeta potential, and drug entrapment, presenting the most stable and deformable vesicle system. In vitro drug release (83.26 ± 1.27%) was significantly greater in the optimized formula compared to the NLT suspension. NLT-SPL showed oral bioavailability 2.5 times higher than the NLT suspension, prolonged drug Tmax, and sustained plasma drug concentrations. NLT-SPL also exhibited superior cytotoxicity to HL-60 and HEL cells as well as higher Caco-2 permeability than the free NLT. NLT-SPL significantly enhanced the oral bioavailability and its anti-leukemic activity. This nanocarrier approach avoids NLT’s solubility problems, presenting a potential framework to improve CML therapeutic results.
Hamzah et al. (Thu,) studied this question.