Enhanced oral bioavailability of Tanshinone IIA using lipid nanocapsules: Formulation, in-vitro appraisal and pharmacokinetics

Ashour, Asmaa A.; Ramadan, Alyaa; Abdelmonsif, Doaa A.; El-Kamel, Amal H.

doi:10.1016/j.ijpharm.2020.119598

Cited by 45 publications

(37 citation statements)

References 42 publications

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“…The results showed that the absorption rate and degree of TSA-LNC were significantly higher than those of TSA suspension. In addition, the half-life and average residence time of TSA-LNC increased significantly [97]. Wang et al combined TSN and TMP into a composite material and prepared oil-in-water nanoemulsions to extend the circulation time in vivo and in vitro and improve the bioavailability of TSN [98].…”

Section: Anti-ischemic Effects and Mechanisms Of Rg1 Rg1mentioning

confidence: 99%

Classical Active Ingredients and Extracts of Chinese Herbal Medicines: Pharmacokinetics, Pharmacodynamics, and Molecular Mechanisms for Ischemic Stroke

Zhu

Wang²,

Feng³

et al. 2021

Oxidative Medicine and Cellular Longevity

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Stroke is a leading cause of death and disability worldwide, and approximately 87% of cases are attributed to ischemia. The main factors that cause ischemic stroke include excitotoxicity, energy metabolism disorder, Ca+ overload, oxidative damage, apoptosis, autophagy, and inflammation. However, no effective drug is currently available for the comprehensive treatment of ischemic stroke in clinical applications; thus, there is an urgent need to find and develop comprehensive and effective drugs to treat postischemic stroke. Traditional Chinese medicine (TCM) has unique advantages in treating ischemic stroke, with overall regulatory effects at multiple levels and on multiple targets. Many researchers have studied the effective components of TCMs and have achieved undeniable results. This paper reviews studies on the anticerebral ischemia effects of TCM monomers such as tetramethylpyrazine (TMP), dl-3-n-butylphthalide (NBP), ginsenoside Rg1 (Rg1), tanshinone IIA (TSA), gastrodin (Gas), and baicalin (BA) as well as effective extracts such as Ginkgo biloba extract (EGB). Research on the anticerebral ischemia effects of TCMs has focused mostly on their antioxidative stress, antiapoptotic, anti-inflammatory, proangiogenic, and proneurogenic effects. However, the research on the use of TCM to treat ischemic stroke remains incompletely characterized. Thus, we summarized and considered this topic from the perspective of pharmacokinetics, pharmacological effects, and mechanistic research, and we have provided a reference basis for future research and development on anticerebral ischemia TCM drugs.

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Section: Anti-ischemic Effects and Mechanisms Of Rg1 Rg1mentioning

confidence: 99%

Classical Active Ingredients and Extracts of Chinese Herbal Medicines: Pharmacokinetics, Pharmacodynamics, and Molecular Mechanisms for Ischemic Stroke

Zhu

Wang²,

Feng³

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…It had a wide tissue distribution but the oral bioavailability was extremely low ( Bi et al, 2007 ). Improving the type of preparation, such as the use of lipid nanocapsules ( Ashour et al, 2020 ) or interactions among different active components of S. miltiorrhiza and herb-drug interactions can increase the bioavailability and plasma concentrations of Tan IIA obviously. For example, compared with oral administration of pure Tan IIA, the AUC 0-∞ of Tan IIA was significantly higher in the prostate, liver, and heart of rats receiving Salvia miltiorrhiza extract ( Wang D. et al, 2020 ).…”

Section: Basic Propertiesmentioning

confidence: 99%

Recent Research Progress (2015–2021) and Perspectives on the Pharmacological Effects and Mechanisms of Tanshinone IIA

Zhong

Lin

et al. 2021

Front. Pharmacol.

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Tanshinone IIA (Tan IIA) is an important characteristic component and active ingredient in Salvia miltiorrhiza, and its various aspects of research are constantly being updated to explore its potential application. In this paper, we review the recent progress on pharmacological activities and the therapeutic mechanisms of Tan IIA according to literature during the years 2015–2021. Tan IIA shows multiple pharmacological effects, including anticarcinogenic, cardiovascular, nervous, respiratory, urinary, digestive, and motor systems activities. Tan IIA modulates multi-targets referring to Nrf2, AMPK, GSK-3β, EGFR, CD36, HO-1, NOX4, Beclin-1, TLR4, TNF-α, STAT3, Caspase-3, and bcl-2 proteins and multi-pathways including NF-κB, SIRT1/PGC1α, MAPK, SREBP-2/Pcsk9, Wnt, PI3K/Akt/mTOR pathways, TGF-β/Smad and Hippo/YAP pathways, etc., which directly or indirectly influence disease course. Further, with the reported targets, the potential effects and possible mechanisms of Tan IIA against diseases were predicted by bioinformatic analysis. This paper provides new insights into the therapeutic effects and mechanisms of Tan IIA against diseases.

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“…Finally, the LNC dispersion formed was subjected to slow magnetic stirring for 5 minutes, followed by filtration through a 0.45 μm Millipore syringe filter. 21 PS-LNCs was prepared by addition of PS (0.25%-0.5% w/v of the final dispersion) to other LNC ingredients at the beginning of the process. The same method of preparation of blank LNCs was adopted, except for raising the temperature in the first cycle to 70°C to ensure complete melting of PS.…”

Section: Preparation Of Lncsmentioning

confidence: 99%

“…[18][19][20] Recently, TSIIA-loaded LNCs were successfully prepared by our research team and reported to greatly enhance its oral bioavailability. 21 Targeting various receptors expressed on the surface of activated HSCs and KCs is the mainstay of effective management of liver fibrosis. Accordingly, hyaluronic acid (HA) 22,23 and vitamin A 24,25 have been exploited to achieve active targeting to HSCs.…”

Section: Introductionmentioning

confidence: 99%

Modified Lipid Nanocapsules for Targeted Tanshinone IIA Delivery in Liver Fibrosis

Ashour¹,

El-Kamel²,

Abdelmonsif³

et al. 2021

IJN

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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.

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Enhanced oral bioavailability of Tanshinone IIA using lipid nanocapsules: Formulation, in-vitro appraisal and pharmacokinetics

Cited by 45 publications

References 42 publications

Classical Active Ingredients and Extracts of Chinese Herbal Medicines: Pharmacokinetics, Pharmacodynamics, and Molecular Mechanisms for Ischemic Stroke

Classical Active Ingredients and Extracts of Chinese Herbal Medicines: Pharmacokinetics, Pharmacodynamics, and Molecular Mechanisms for Ischemic Stroke

Recent Research Progress (2015–2021) and Perspectives on the Pharmacological Effects and Mechanisms of Tanshinone IIA

Modified Lipid Nanocapsules for Targeted Tanshinone IIA Delivery in Liver Fibrosis

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