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Kiwi-derived extracellular vesicles for oral delivery of sorafenib
Zhou Fang1, Mengdi Song1, Keqiang Lai2
1Department of Biopharmaceutical Science, Shanghai Ocean University, Hucheng Ring Road, Shanghai 201306, China; Marine Biomedical Science and Technology Innovation Platform of Lin-gang Special Area, Shanghai 201306, China.
Abstract:
Sorafenib is an oral treatment for hepatocellular carcinoma (HCC). However, poor water solubility, harsh gastrointestinal environment and off-target effects contribute to the low bioavailability of oral sorafenib. Plant-derived extracellular vesicles (PDEVs) are biological nanovesicles with various bioactive functions that offer significant advantages in the field of oral drug delivery: protection from degradation by gastrointestinal fluids; crossing the intestinal epithelial barrier; specific targeting; safety; and abundant yield. However, there are fewer studies applying PDEVs for anti-tumor drug delivery to extra-digestive tissues. In this study, kiwifruit-derived extracellular vesicles (KEVs) were isolated and purified from kiwifruit, and their natural hepatic accumulation properties were exploited for targeted delivery of sorafenib (KEVs-SFB). Evidence showed that encapsulation of KEVs reduced the leakage of sorafenib in the gastrointestinal environment and enhanced the ability to cross the intestinal epithelium; KEVs-SFB was able to achieve liver accumulation and was predominantly taken up by HepG2 cells; KEVs-SFB was effective in inhibiting 4T1 cell proliferation; in the orthotopic liver cancer model, oral administration of KEVs-SFB inhibited tumor growth and improved the side effects of SFB. This PDEVs-based oral drug delivery platform is important for improving oral bioavailability and reducing drug side effects.
Insights
Kiwifruit-derived extracellular vesicles (KEVs) loaded with sorafenib (KEVs-SFB) improve oral drug delivery for liver cancer. This novel platform enhances bioavailability and reduces side effects, offering a promising approach for hepatocellular carcinoma treatment.
Area of Science:
- Biotechnology
- Nanomedicine
- Drug Delivery
Background:
- Oral sorafenib for hepatocellular carcinoma (HCC) faces challenges like poor solubility, gastrointestinal degradation, and off-target effects, limiting its bioavailability.
- Plant-derived extracellular vesicles (PDEVs) show potential for oral drug delivery due to their protective, barrier-crossing, targeting, and safety advantages.
Purpose of the Study:
- To develop a targeted oral drug delivery system for sorafenib using kiwifruit-derived extracellular vesicles (KEVs).
- To evaluate the efficacy of KEVs-encapsulated sorafenib (KEVs-SFB) in improving oral bioavailability and reducing side effects in liver cancer models.
Main Methods:
- Isolation and purification of kiwifruit-derived extracellular vesicles (KEVs).
- Encapsulation of sorafenib into KEVs to create KEVs-SFB.
- Assessment of KEVs-SFB's stability in the gastrointestinal environment and intestinal permeability.
- Evaluation of liver accumulation and cellular uptake in HepG2 cells.
- In vitro assessment of anti-proliferative effects on 4T1 cells.
- In vivo study using an orthotopic liver cancer model to evaluate tumor inhibition and side effects.
Main Results:
- KEVs encapsulation protected sorafenib from gastrointestinal degradation and enhanced intestinal epithelial barrier crossing.
- KEVs-SFB demonstrated significant liver accumulation and preferential uptake by HepG2 cells.
- KEVs-SFB effectively inhibited 4T1 cell proliferation in vitro.
- Oral administration of KEVs-SFB suppressed tumor growth and ameliorated sorafenib-induced side effects in an orthotopic liver cancer model.
Conclusions:
- Plant-derived extracellular vesicles, specifically KEVs, represent a viable platform for enhancing oral drug delivery of sorafenib for hepatocellular carcinoma.
- The KEVs-based delivery system improves sorafenib's oral bioavailability, targets the liver, and reduces adverse effects, offering a promising therapeutic strategy.
