ABSTRACT Nilotinib, a potent BCR‐ABL tyrosine kinase inhibitor, suffers from poor aqueous solubility, limited dissolution, and inadequate intestinal permeability, thereby restricting its oral bioavailability and broader therapeutic applicability in solid tumors. This study aimed to develop and optimize a PEGylated, lyophilized nanoliposomal formulation to overcome these biopharmaceutical limitations and to enhance the biopharmaceutical performance and in vitro anticancer activity of nilotinib. Fifteen formulations (F1–F15) were prepared by thin‐film hydration followed by probe sonication, employing varying ratios of phosphatidylcholine, cholesterol, DSPE‐PEG2000, and trehalose as cryoprotectant. Preliminary physicochemical screening identified F10 as the optimized formulation, exhibiting a particle size of 142. 3 ± 4. 8 nm, polydispersity index of 0. 182, zeta potential of –32. 6 ± 2. 1 mV, and an entrapment efficiency of 88. 4 ± 2. 6%. Transmission electron microscopy confirmed spherical vesicular morphology, while Fourier‐transform infrared, differential scanning calorimetry, and X‐ray diffraction analyses demonstrated drug–excipient compatibility and complete amorphization of nilotinib within the lipid bilayer. In vitro release studies revealed significantly enhanced and sustained drug release from F10 compared with pure nilotinib. Ex vivo intestinal permeation showed a 3. 6‐fold increase in cumulative permeation and markedly higher apparent permeability (Pₐpp = 5. 82 × 10 − 5 cm/s) relative to the pure drug. Biological evaluation using MCF‐7 breast cancer cells demonstrated substantially improved cytotoxicity (50% inhibitory concentration = 6. 7 µg/mL), enhanced reactive oxygen species generation, pronounced mitochondrial membrane depolarization, stronger apoptosis induction, and significant G0/G1‐phase arrest compared with the pure drug. Collectively, these findings demonstrate that the optimized PEGylated nanoliposomal formulation significantly improves solubility, stability, intestinal permeation, and in vitro anticancer activity of nilotinib, supporting its potential as a promising preclinical formulation strategy for further in vivo and clinical evaluation.
Singh et al. (Tue,) studied this question.