PEGylated hyaluronic acid-coated liposome for enhanced in vivo efficacy of sorafenib via active tumor cell targeting and prolonged systemic exposure.

This study aimed to design an effective formulation for enhancing the tumor-targeted delivery of sorafenib. Three sorafenib-loaded liposomal formulations including uncoated liposome (SF-Lip), hyaluronic acid-coated liposome (HA-SF-Lip), and PEGylated hyaluronic acid-coated liposome (PEG-HA-SF-Lip) were developed with narrow size distribution and high encapsulation efficiency. The cellular uptake and cytotoxicity of HA-SF-Lip and PEG-HA-SF-Lip were greater than those of SF-Lip in MDA-MB-231 cells overexpressing CD44, whereas there were no significant differences in MCF-7 cells with low CD44 expression, indicating the CD44-mediated cellular uptake of coated liposomes. In comparison with sorafenib solution, PEG-HA-SF-Lip increased the systemic exposure and plasma half-life in rats by 3-fold and 2-fold, respectively. Consistently, PEG-HA-SF-Lip was the most effective for tumor growth inhibition through CD44 targeting in the MDA-MB-231 tumor xenograft mouse model. Taken together, the present study suggests that PEG-HA-SF-Lip might be effective for the tumor-targeted delivery of sorafenib with enhanced systemic exposure and longer blood circulation.

Bioresorbable Multilayer Organic-Inorganic Films for Bioelectronic Systems.

Bioresorbable electronic devices as temporary biomedical implants represent an emerging class of technology relevant to a range of patient conditions currently addressed with technologies that require surgical explantation after a desired period of use. Obtaining reliable performance and favorable degradation behavior demands materials that can serve as biofluid barriers in encapsulating structures that avoid premature degradation of active electronic components. Here, this work presents a materials design that addresses this need, with properties in water impermeability, mechanical flexibility, and processability that are superior to alternatives. The approach uses multilayer assemblies of alternating films of polyanhydride and silicon oxynitride formed by spin-coating and plasma-enhanced chemical vapor deposition , respectively. Experimental and theoretical studies investigate the effects of material composition and multilayer structure on water barrier performance, water distribution, and degradation behavior. Demonstrations with inductor-capacitor circuits, wireless power transfer systems, and wireless optoelectronic devices illustrate the performance of this materials system as a bioresorbable encapsulating structure.

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

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.