Modified Lipid Nanocapsules for Targeted Tanshinone IIA Delivery in Liver Fibrosis

Abstract

Introduction:Liver fibrosis represents a serious global disease with no approved treatment. Tanshinone IIA (TSIIA) is a phytomedicine with documented activity in treating many hepatic disorders. TSIIA has been reported to have potent anti-inflammatory and antioxidant properties. It can also induce apoptosis for activated hepatic stellate cells, and is thereby considered as a promising herbal remedy for treating fibrotic liver. However, its poor aqueous solubility, short half-life, exposure to the first-pass effect, and low concentration reaching targeted cells constitute the major barriers hindering its effective therapeutic potential. Therefore, this work aimed at enhancing TSIIA systemic bioavailability together with achieving active targeting potential to fibrotic liver via its incorporation into novel modified lipid nanocapsules (LNCs). Methods: Blank and TSIIA-loaded LNCs modified with either hyaluronate sodium or phosphatidyl serine were successfully prepared, optimized, and characterized both in vitro and in vivo. Results:The developed LNCs showed good colloidal properties (size ≤100 nm and PDI ≤0.2), high drug-entrapment efficiency (>97%) with sustained-release profile for 24 hours, high storage stability up to 6 months, and good in vitro serum stability. After a single intraperitoneal injection, the administered LNCs exhibited a 2.4-fold significant increase in AUC 0-∞ compared with the TSIIA suspension (p≤0.01). Biodistribution-study results proved the liver-targeting ability of the prepared modified LNCs, with a significant ~1.5-fold increase in hepatic accumulation compared with the unmodified formulation (p≤0.05). Moreover, the modified formulations had an improved antifibrotic effect compared with both unmodified LNCs and TSIIA suspension, as evidenced by the results of biochemical and histopathological evaluation. Conclusion:The modified TSIIA-LNCs could be regarded as promising novel targeted nanomedicines for effective management of liver fibrosis.

Luteolin-loaded exosomes derived from bone marrow mesenchymal stem cells: a promising therapy for liver fibrosis

“…Coumarin-6 was observed through the green channel at an excitation wavelength of 485 nm while Hoechst-nuclear counter stain was observed through the blue channel at 430 nm. Finally, the fluorescence intensity in the obtained images was quantified using Image J software (version 1.45 s) as previously described (Ashour et al., 2021 ; Shehata et al., 2022 ).…”

“…Up till now, there is no treatment for liver fibrosis and elimination of the etiological factors represents the adopted strategy for therapy. Currently, many antifibrotic drugs are in different phases of clinical trials and none of them was finally approved for clinical use (Ashour et al., 2021 ). This necessitates finding new therapeutic options for effective disease management.…”

Tanshinone IIA loaded bioactive nanoemulsion for alleviation of lipopolysaccharide induced acute lung injury via inhibition of endothelial glycocalyx shedding

“…Release of TSIIA from the selected NE formulation was investigated by the dialysis method [15] . TSIIA-NE (1 ml equivalent to 250 μg TSIIA) was placed in presoaked dialysis bags (VISKING® dialysis tubing MWCO 12,000–14,000), which were then immersed in 20 ml release medium (ethanol: water, 1:1) maintaining sink conditions.…”

“…Previous work has demonstrated its ability to alleviate ALI induced by lipopolysaccharide (LPS) either for prophylaxis [13] or treatment [14] . However, its therapeutic activity is limited owing to low aqueous solubility, poor bioavailability, short half-life, and extensive metabolism [15] .…”

“…Several nano-technology based delivery systems were elaborated in the literature allowing for the formation of stable colloidal dispersion thus overcoming poor solubility and attempting to enhance bioavailability and protect the drug from metabolic enzymes [15] , [16] , [17] , [18] , [19] , [20] . Due to the hydrophobic nature of the drug, a lipid-based delivery system is expected to allow for increased drug loading and enhanced systemic bioavailability.…”