Optimizing gefitinib nanoliposomes by Box-Behnken design and coating with chitosan: A sequential approach for enhanced drug delivery

Background and purpose: This study aimed to improve the stability and prolonged gefitinib release from the nanoliposomes.

Experimental approach: Nanoliposomes were prepared by reverse-phase evaporation and optimized using Box-Behnken design to investigate the influence of sonication time (X ₁), tween 80 / soya phosphatidylcholine ratio (X ₂), and cholesterol/soya phosphatidylcholine ratio (X ₃) on nanoliposomes.

Key results: Optimized nanoliposomes were quasi-spherical shaped, with a mean dimension of 93.2 nm and an encapsulation efficiency of 87.56±0.17 %. Surface decoration of the optimized batch was done using different concentrations of chitosan. The optimal chitosan concentration required to adorn the nanoliposome surface was 0.01 %. In comparison to unadorned nanoliposomes (82.16±0.65 %), adorned nanoliposomes (78.04±0.35 %) released the drug consistently over 24 h via Fickian diffusion. The IC₅₀ values for surface-adorned nanoliposomes in A549 and H1299 cells were 6.53±0.75 and 4.73±0.46 μM, respectively. Cytotoxicity of the surface-decorated nanoliposomes may be due to their higher zeta potential and prolonged drug release. At the end of the sixth month, the samples stored at 4 °C were more stable than those stored at 25 °C and 45 °C. The stability of plain nanoliposomes has increased after chitosan coating. Thus, by using different concentrations of chitosan solution as coating material, we can develop a suitable sustained drug-release surface-adorned nanoliposomal formulation.

Conclusion: The developed nanoliposomes may offer a new path for melanoma clinics.