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

S. Rohilla,R. Awasthi,A. Rohilla,S. Singh,D. Chellappan,K. Dua,H. Dureja

Published 2024 in ADMET and DMPK

ABSTRACT

Abstract 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 (X1), tween 80 / soya phosphatidylcholine ratio (X2), and cholesterol/soya phosphatidylcholine ratio (X3) 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.

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