Neutrophil-Based Bionic Delivery System Breaks Through the Capillary Barrier of Liver Sinusoidal Endothelial Cells and Inhibits the Activation of Hepatic Stellate Cells.

The capillarization of hepatic sinusoids resulting from the activation of hepatic stellate cells poses a significant challenge, impeding the effective delivery of therapeutic agents to the Disse space for liver fibrosis treatment. Therefore, overcoming these barriers and achieving efficient drug delivery to activated hepatic stellate cells (aHSCs) are pressing challenge. In this study, we developed a synergistic sequential drug delivery approach utilizing neutrophil membrane hybrid liposome@atorvastatin/amlisentan (NCM@AtAm) and vitamin A-neutrophil membrane hybrid liposome @albumin (VNCM@Bai) nanoparticles (NPs) to breach the capillary barrier for targeted HSC cell delivery. Initially, NCM@AtAm NPs were successfully directed to the site of hepatic fibrosis through neutrophil-mediated inflammatory targeting, resulting in the normalization of liver sinusoidal endothelial cells (LSECs) and restoration of fenestrations under the combined influence of At and Am. Elevated tissue levels of the p-Akt protein and endothelial nitric oxide synthase (eNOS) indicated the normalization of LSECs following treatment with At and Am. Subsequently, VNCM@Bai NPs traversed the restored LSEC fenestrations to access the Disse space, facilitating the delivery of Bai into aHSCs under vitamin A guidance. Lastly, both in vitro and in vivo results demonstrated the efficacy of Bai in inhibiting HSC cell activation by modulating the PPAR γ/TGF-ß1 and STAT1/Smad7 signaling pathways, thereby effectively treating liver fibrosis. Overall, our designed synergistic sequential delivery system effectively overcomes the barrier imposed by LSECs, offering a promising therapeutic strategy for liver fibrosis treatment in clinical settings.

Hydroxypropyl Cellulose-Based Orally Dissolving Film Loaded with Insoluble Dexamethasone for Treatment of Oral Ulcers.

Oral ulcers present as recurrent and spontaneous lesions, often causing intolerable burning pain that significantly disrupts patients' daily lives and compromises their quality of life. In addressing this clinical challenge, oral dissolving films (ODFs) have emerged as promising pharmaceutical formulations for oral ulcer management due to their rapid onset of action, ease of administration, and portability. In this study, ODFs containing the insoluble drug dexamethasone (Dex) were formulated for the treatment of oral ulcers in rabbits using a solvent casting method with ethanol as the solvent. To optimize the composition of the ODFs, a Box-Behnken Design (BBD) experiment was employed to investigate the effects of varying concentrations of hydroxypropyl cellulose (HPC), low-substituted hydroxypropyl cellulose (L-HPC), and plasticizer (glycerol) on key parameters, such as disintegration time, tensile strength, and peel-off efficiency of the films. Subsequently, the film properties of the Dex-loaded ODFs (ODF@Dex) were thoroughly assessed, revealing favorable attributes, including homogeneity, mechanical strength, and solubility. Notably, the use of ethanol as the solvent in the ODF preparation facilitated the homogeneous distribution of insoluble drugs within the film matrix, thereby enhancing their solubility and dissolution rate. Leveraging the potent pharmacological activity of Dex, ODF@Dex was further evaluated for its efficacy in promoting ulcer healing and mitigating the expression of inflammatory factors both in vitro and in vivo. The findings demonstrated that the ODF@Dex exerted significant antiulcer effects by modulating the PI3K/Akt signaling pathway, thus contributing to ulcer resolution. In conclusion, our study underscores the potential of HPC-based ODFs formulated with ethanol as a solvent as a promising platform for delivering insoluble drugs, offering a viable strategy for the clinical management of oral ulcers.