Oral vitamin-A-coupled valsartan nanomedicine: High hepatic stellate cell receptors accessibility and prolonged enterohepatic residence

El–Mezayen, Nesrine S.; El-Hadidy, Wessam F.; El-Refaie, Wessam M.; Shalaby, Thanaa I.; Khattab, Mahmoud M.; El-Khatib, Aiman S.

doi:10.1016/j.jconrel.2018.05.021

Cited by 31 publications

(30 citation statements)

References 64 publications

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“…Aside from manipulating atRA-signaling to reduce fibrosis, several interesting approaches rely on the retinol storage property of HSCs and PSCs to efficiently deliver antifibrotic drugs and siRNAs to HSCs and PSCs (El-Mezayen et al, 2018;Okimoto et al, 2019;Qiao et al, 2018;Sato et al, 2008;Z. Zhang et al, 2015).…”

Section: Role Of Atra In the Development And Function Of Hepatic And Pancreatic Stellate Cellsmentioning

confidence: 99%

Modulation of retinoid signaling: therapeutic opportunities in organ fibrosis and repair

Wang

Kane

et al. 2020

Pharmacology & Therapeutics

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The vitamin A metabolite, retinoic acid, is an important signaling molecule during embryonic development serving critical roles in morphogenesis, organ patterning and skeletal and neural development. Retinoic acid is also important in postnatal life in the maintenance of tissue homeostasis, while retinoid-based therapies have long been used in the treatment of a variety of cancers and skin disorders. As the number of people living with chronic disorders continues to increase, there is great interest in extending the use of retinoid therapies in promoting the maintenance and repair of adult tissues. However, there are still many conflicting results as we struggle to understand the role of retinoic acid in the multitude of processes that contribute to tissue injury and repair. This review will assess our current knowledge of the role retinoic acid signaling in the development of fibroblasts, and their transformation to myofibroblasts, and of the potential use of retinoid therapies in the treatment of organ fibrosis.

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Section: Role Of Atra In the Development And Function Of Hepatic And Pancreatic Stellate Cellsmentioning

confidence: 99%

Modulation of retinoid signaling: therapeutic opportunities in organ fibrosis and repair

Wang

Kane

et al. 2020

Pharmacology & Therapeutics

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“…The nanoformulations not only inhibited the expression of phosphorylated PDGFR-β but also reduced the expression of profibrotic mediators such as hydroxyproline, TGF-β, and MMP2 with fewer adverse effects. In another study, VA-coupled liposomes were used to deliver valsartan, an angiotensin II receptor antagonist [ 89 ]. The nanoformulations increased the expression of hepatic Mas-receptor and PPAR-γ and potently normalized the level of fibrogenic mediators by improving the permeability and efficacy of valsartan.…”

Section: Nanomedicine For Liver Fibrosis Therapymentioning

confidence: 99%

Recent Advances in Nanomedicine for the Diagnosis and Therapy of Liver Fibrosis

Bai

Zhai

2020

Nanomaterials

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Liver fibrosis, a reversible pathological process of inflammation and fiber deposition caused by chronic liver injury and can cause severe health complications, including liver failure, liver cirrhosis, and liver cancer. Traditional diagnostic methods and drug-based therapy have several limitations, such as lack of precision and inadequate therapeutic efficiency. As a medical application of nanotechnology, nanomedicine exhibits great potential for liver fibrosis diagnosis and therapy. Nanomedicine enhances imaging contrast and improves tissue penetration and cellular internalization; it simultaneously achieves targeted drug delivery, combined therapy, as well as diagnosis and therapy (i.e., theranostics). In this review, recent designs and development efforts of nanomedicine systems for the diagnosis, therapy, and theranostics of liver fibrosis are introduced. Relative to traditional methods, these nanomedicine systems generally demonstrate significant improvement in liver fibrosis treatment. Perspectives and challenges related to these nanomedicine systems translated from laboratory to clinical use are also discussed.

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“…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. Phosphatidyl serine (PS) was previously regarded as a targeting ligand to KCs.…”

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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Oral vitamin-A-coupled valsartan nanomedicine: High hepatic stellate cell receptors accessibility and prolonged enterohepatic residence

Cited by 31 publications

References 64 publications

Modulation of retinoid signaling: therapeutic opportunities in organ fibrosis and repair

Modulation of retinoid signaling: therapeutic opportunities in organ fibrosis and repair

Recent Advances in Nanomedicine for the Diagnosis and Therapy of Liver Fibrosis

Modified Lipid Nanocapsules for Targeted Tanshinone IIA Delivery in Liver Fibrosis

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