M6P-modified solid lipid nanoparticles loaded with matrine for the treatment of fibrotic liver

Abstract

Liver fibrosis is a key pathological process shared by the progression of various chronic liver diseases. Treatment of liver fibrosis can effectively block the occurrence and development of hepatic cirrhosis or even carcinoma. Currently, there is no effective drug delivery vehicle for curing liver fibrosis. In this study, we designed matrine (MT)-loaded mannose 6-phosphate (M6P) modified human serum albumin (HSA) conjugated solid lipid nanoparticles (SLN), named M6P-HSA-MT-SLN for treatment of hepatic fibrosis. We demonstrated that M6P-HSA-MT-SLN exhibited controlled and sustained release properties and good stability over 7 days. The drug release experiments showed that M6P-HSA-MT-SLN exhibited slow and controlled drug release characteristics. In addition, M6P-HSA-MT-SLN showed a significant targeted ability to fibrotic liver. Importantly, in vivo studies indicated that M6P-HSA-MT-SLN could significantly improve histopathological morphology and inhibit the fibrotic phenotype. In addition, in vivo experiments demonstrate that M6P-HSA-MT-SLN could reduce the expression of fibrosis markers and alleviate the damage of liver structure. Hence, the M6P-HSA-MT-SLN provide a promising strategy to deliver therapeutic agents to fibrotic liver to prevent liver fibrosis.

Combined Amphiphilic Silybin Meglumine Nanosuspension Effective Against Hepatic Fibrosis in Mice Model

“…9,10 To overcome these limitations, nanopreparation strategies have been applied to formulate these compounds into liposomes, nano-emulsions, inclusion compounds, and nanoparticles. [11][12][13] Alya, et al 14 made significant efforts to load curcumin into silver nanoparticles, which showed satisfying anti-liver fibrosis activity and confirmed the fact that nanopreparations have a size benefit against liver fibrosis. Li, et al 3 reported a nanomicelle strategy to load silybin, which showed significant liver targeting effect.…”

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“…In their experiments, it was observed that M6P-guided SLNs demonstrated a predilection for accumulation in fibrotic livers and exhibited reduced metabolic rates, suggesting an augmentation in targeted drug delivery and improved bioavailability. 53 Nanostructured lipid carriers (NLCs) represent the subsequent iteration of drug delivery systems, surpassing liposomes and presenting improved drug safeguarding and targeting functionalities. Diverging from solid lipid carriers (SLCs), NLCs employ a distinctive lipid structure that integrates both solid and liquid lipids, which enhances drug stability and significantly increases the drug-loading capacity.…”

“…In their experiments, it was observed that M6P-guided SLNs demonstrated a predilection for accumulation in fibrotic livers and exhibited reduced metabolic rates, suggesting an augmentation in targeted drug delivery and improved bioavailability. 53…”

Exploring the potential role of genus Sophora in the management of osteoporosis: a phytochemical and biological review

“…It showed various pharmacological effects, including anti-inflammatory, anti-tumor, and antiviral activities (Zhang et al, 2019;Luo et al, 2021;Liu J. et al, 2022). It demonstrated anti-fibrotic action by inhibiting the TGF-β/Smad pathway in liver, cardiac, and pancreatic fibrosis (Tan et al, 2023). Additionally, Mao et al showed that inhibiting the TGF-β/Smad pathway is a possible treatment for heterotopic ossification (HO) by inducing mesenchymal stem cell (MSC) migration and osteogenic differentiation (Mao et al, 2020).…”