Development and Optimization of Nanostructured Lipid Carriers of Nilotinib for Treatment of Cancer via Oral Route

Background/Objectives: Nilotinib (NTB) a tyrosine kinase inhibitor, helps CML patients with the Philadelphia chromosome. An increasingly rigorous dose regimen and a boxed warning limit the drug's use. NTB should be taken orally on an empty stomach two hours before and one hour after the dosage. A new reduced-dose nanoparticle formulation of NTB reduces the effect of food on PK and achieves equivalent bioavailability (BA) while fasting. The study investigated if nanostructured lipid carriers could make BCS class II medication NTB more soluble and easier to swallow. Methods: The formulation was optimized using the "Box-Behnken design (3-factor, 3-level)". Polydispersity index, Zeta potential, EE, and particle size were dependent variables, while total lipid concentration, surfactant concentration, and sonication time were independent. Investigation of the optimized formulation's in vivo pharmacokinetics, tissue absorption, and in vitro release. Results: In the optimized formulation, PDI, particle size, EE%, and ZP were 135.26±3.86 nm, 0.126±0.09, 89.62±1.26%, and -42.16±1.75mV, respectively. Transmission electron microscopy revealed circular particles. In vitro, NTB released 96.15% with pure NTB dispersion and 56.34% with NTB-NLCs after 24 hours. The data was acquired using a zero order. NTB was ad-ministered to acute myeloid, acute lymphoblastic, and acute T cell leukaemia at IC50 values of 251, 302, 398, 218, 248, and 225 µg/mL, respectively. NTB had IC50 values of 124, 118, 146, 125, 139, and 135 µg/mL against acute myeloid, acute lymphoblastic, and acute T cell leukaemia cell lines. Conclusions: The malignant leukaemia cell line's vitality decreased dose-dependently with NLCs and NTB. Our cytotoxicity experiments in various cell lines and Wistar rats enhanced oral bioavailability of NTB suggest that the optimized NTB-loaded NLCs.