Enhanced oral absorption of sorafenib via the layer-by-layer deposition of a pH-sensitive polymer and glycol chitosan on the liposome

초록

This study aimed to design the effective formulation of sorafenib (SF) to enhance the oral drug absorption. Three liposomal formulations of SF were prepared including uncoated liposome (SF-Lip), glycol chitosan-coated liposome (GC-SF-Lip), and Eudragit S100-glycol-chitosan coated liposome (SGC-SF-Lip). All formulations showed a narrow size distribution with a high encapsulation efficiency. Both GC-SF-Lip and SGC-SF-Lip exhibited good stability at acidic and neutral pHs without any significant drug leakage, while SF-Lip appeared to be unstable at pH 1.2. In the case of double coated SGC-SF-Lip, its size changed significantly at pH 7.4, due to the dissolution of Eudragit S100 coating layer into the surrounding medium. Compared to SF solution, all liposomal formulations demonstrated a higher cellular uptake in Caco-2 cells. In particular, SGC-SF-Lip displayed a lower cellular uptake than GC-SF-Lip at pH 6.5, but it achieved a similar cellular uptake to GC-SF-Lip at pH 7.4. Consistently, SGC-SF-Lip was less cytotoxic than GC-SF-Lip at pH 6.5, whereas it showed a comparable cytotoxicity to GC-SF-Lip at pH 7.4, implying the removal of the Eudragit S100 coating layer at pH 7.4. After an oral administration to rats, SGC-SF-Lip significantly improved the systemic exposure of SF, where its Cmax and AUC were approximately fourfold higher than the untreated drug. Collectively, SGC-SF-Lip appeared to be promising to enhance the oral absorption of SF.

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