The diosgenin prodrug nanoparticles with pH-responsive as a drug delivery system uniquely prevents thrombosis without increased bleeding risk

Wei, Zeliang; Xin, Guang; Wang, Haibo; Zheng, Heng; Ji, Chengjie; Gu, Jun; Ma, Limei; Qin, Chaoyi; Xing, Zhihua; Niu, Hai; Huang, Wen

doi:10.1016/j.nano.2017.12.019

Cited by 44 publications

(29 citation statements)

References 49 publications

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“…It has been reported that hyaluronate-DG conjugation via esterification can promote self-assembly into stable, negatively charged nanoparticles measuring 159-441 nm in water, which significantly enhances its solubility [62]. The DG-PEG conjugate can self-assemble into micelles in water, thus significantly enhancing the therapeutic efficacy for the prevention of arterial thrombus and venous thrombus [63].…”

Section: Novel Formulations and Increasedmentioning

confidence: 99%

Therapeutic Potential of Diosgenin and Its Major Derivatives against Neurological Diseases: Recent Advances

Cai

Zhang

Wang

et al. 2020

Oxidative Medicine and Cellular Longevity

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Diosgenin (DG), a well-known steroidal sapogenin, is present abundantly in medicinal herbs such as Dioscorea rhizome, Dioscorea villosa, Trigonella foenum-graecum, Smilax China, and Rhizoma polgonati. DG is utilized as a major starting material for the production of steroidal drugs in the pharmaceutical industry. Due to its wide range of pharmacological activities and medicinal properties, it has been used in the treatment of cancers, hyperlipidemia, inflammation, and infections. Numerous studies have reported that DG is useful in the prevention and treatment of neurological diseases. Its therapeutic mechanisms are based on the mediation of different signaling pathways, and targeting these pathways might lead to the development of effective therapeutic agents for neurological diseases. The present review mainly summarizes recent progress using DG and its derivatives as therapeutic agents for multiple neurological disorders along with their various mechanisms in the central nervous system. In particular, those related to therapeutic efficacy for Parkinson’s disease, Alzheimer’s disease, brain injury, neuroinflammation, and ischemia are discussed. This review article also critically evaluates existing limitations associated with the solubility and bioavailability of DG and discusses imperatives for translational clinical research. It briefly recapitulates recent advances in structural modification and novel formulations to increase the therapeutic efficacy and brain levels of DG. In the present review, databases of PubMed, Web of Science, and Scopus were used for studies of DG and its derivatives in the treatment of central nervous system diseases published in English until December 10, 2019. Three independent researchers examined articles for eligibility. A total of 150 articles were screened from the above scientific literature databases. Finally, a total of 46 articles were extracted and included in this review. Keywords related to glioma, ischemia, memory, aging, cognitive impairment, Alzheimer, Parkinson, and neurodegenerative disorders were searched in the databases based on DG and its derivatives.

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Section: Novel Formulations and Increasedmentioning

confidence: 99%

Therapeutic Potential of Diosgenin and Its Major Derivatives against Neurological Diseases: Recent Advances

Cai

Zhang

Wang

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…This NC also presents ideal properties to act as a framework for the gene therapy of various target cells in future applications. Another example of a self-assembled polymeric NC can be seen in a Diosgenin pro-drug anti-thrombosis agent where one molecule of the pro-drug is bound to a single PEG chain via a cleavable Schiff bass bond (25). When these monomeric units are placed in solution they self-assemble into PEG micelles that confer enhanced circulation time and controlled release of the prodrug in response to the acidic pH encountered upon arrival to the thrombus site (25).…”

Section: Organic Nanocarriersmentioning

confidence: 99%

“…Another example of a self-assembled polymeric NC can be seen in a Diosgenin pro-drug anti-thrombosis agent where one molecule of the pro-drug is bound to a single PEG chain via a cleavable Schiff bass bond (25). When these monomeric units are placed in solution they self-assemble into PEG micelles that confer enhanced circulation time and controlled release of the prodrug in response to the acidic pH encountered upon arrival to the thrombus site (25). This prodrug facilitates the prevention of arterial and venous thrombus formation by increasing the subsequent Diosgenin therapies bioavailability and attraction to the desired endogenous targets (25).…”

Section: Organic Nanocarriersmentioning

confidence: 99%

“…When these monomeric units are placed in solution they self-assemble into PEG micelles that confer enhanced circulation time and controlled release of the prodrug in response to the acidic pH encountered upon arrival to the thrombus site (25). This prodrug facilitates the prevention of arterial and venous thrombus formation by increasing the subsequent Diosgenin therapies bioavailability and attraction to the desired endogenous targets (25). Another vital group of polymeric NCs are those that are functionalized or composed of the naturally-derived polysaccharide, chitosan.…”

Section: Organic Nanocarriersmentioning

confidence: 99%

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Nanobiotechnology medical applications: Overcoming challenges through innovation

Singer

Markoutsa

Limayem

et al. 2018

The EuroBiotech Journal

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Biomedical Nanotechnology (BNT) has rapidly become a revolutionary force that is driving innovation in the medical field. BNT is a subclass of nanotechnology (NT), and often operates in cohort with other subclasses, such as mechanical or electrical NT for the development of diagnostic assays, therapeutic implants, nano-scale imaging systems, and medical machinery. BNT is generating solutions to many conventional challenges through the development of enhanced therapeutic delivery systems, diagnostic techniques, and theranostic therapies. Therapeutically, BNT has generated many novel nanocarriers (NCs) that each express specifically designed physiochemical properties that optimize their desired pharmacokinetic profile. NCs are also being integrated into nanoscale platforms that further enhance their delivery by controlling and prolonging their release profile. Nano-platforms are also proving to be highly efficient in tissue regeneration when combined with the appropriate growth factors. Regarding diagnostics, NCs are being designed to perform targeted delivery of luminescent tags and contrast agents that enhance the NC -aided imaging capabilities and resulting diagnostic accuracy of the presence of diseased cells. This technology has also been advancing the ability for surgeons to practice true precision surgical techniques. Incorporating therapeutic and diagnostic NC-components within a single NC can facilitate both functions, referred to as theranostics, which facilitates real-time in vivo tracking and observation of drug release events via enhanced imaging. Additionally, stimuli-responsive theranostic NCs are quickly developing as vectors for tumor ablation therapies by providing a model that facilitates the location of cancer cells for the application of an external stimulus. Overall, BNT is an interdisciplinary approach towards health care, and has the potential to significantly improve the quality of life for humanity by significantly decreasing the treatment burden for patients, and by providing non-invasive therapeutics that confer enhanced therapeutic efficiency and safety

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“…Diosgenin is an important steroidal sapogenin and is widely distributed in plants of the Dioscoreae, Liliaceae, Rosaceae and Caryophyllaceae genera and a number of other plants (11). Diosgenin is one of the active ingredients in a variety of Chinese medicines, and it has anti-inflammatory, antidiabetic, antithrombotic, antiallergic and antiviral properties (12)(13)(14)(15)(16). A number of studies have shown that diosgenin inhibits tumor cells by interfering with apoptosis and autophagy of tumor cells (17)(18)(19)(20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

Diosgenin inhibits the epithelial‑mesenchymal transition initiation in osteosarcoma cells via the p38MAPK signaling pathway

Huang

Nie

Qin³

et al. 2019

Oncol Lett

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Diosgenin is an important basic raw material for the production of steroid hormone drugs. It can be isolated and purified from a variety of traditional Chinese medicines or plants. Modern molecular biological studies have shown that diosgenin inhibits various tumor cells migration and invasion ability to varying degrees in vitro and in vivo. The aim of the present study was to observe the inhibitory effects of diosgenin on the invasive and metastatic capabilities of osteosarcoma cells and to determine the association between the effects of diosgenin on the epithelial-mesenchymal transition (EMT). Wound healing and Transwell assays were used to observe the inhibitory effects of diosgenin on the invasion and migration of two osteosarcoma cell lines. Immunofluorescence was used to observe changes in transforming growth factor β1 (TGF-β1) protein expression levels in the osteosarcoma cells following drug administration. EMT-associated proteins, including TGFβ1, E-cadherin and vimentin were detected by western blotting, which demonstrated that the drug may inhibit the initiation of EMT in osteosarcoma cells. Western blot analysis of the expression of all the proteins in the mitogen-activated protein kinase (MAPK) pathway demonstrated that the drug inhibited the MAPK signaling pathway. The primary mechanism of action of diosgenin was the inhibition of the phosphorylated p38 (pP38) protein. Through a combination of inhibitors of the p38MAPK signaling pathway and detection of the downstream EMT marker protein E-cadherin by quantitative PCR, pP38 was confirmed to be a target of diosgenin in the inhibition of EMT in the osteosarcoma cells via the MAPK molecular signaling pathway. Diosgenin may exhibit utility as an auxiliary drug for the clinical reduction of metastasis in patients with osteosarcoma.

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The diosgenin prodrug nanoparticles with pH-responsive as a drug delivery system uniquely prevents thrombosis without increased bleeding risk

Cited by 44 publications

References 49 publications

Therapeutic Potential of Diosgenin and Its Major Derivatives against Neurological Diseases: Recent Advances

Therapeutic Potential of Diosgenin and Its Major Derivatives against Neurological Diseases: Recent Advances

Nanobiotechnology medical applications: Overcoming challenges through innovation

Diosgenin inhibits the epithelial‑mesenchymal transition initiation in osteosarcoma cells via the p38MAPK signaling pathway

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