Release date: 2017-03-28
Recently, Professor Yang Cheng from the School of Pharmacy of Nankai University used phenytoin to promote wound healing. In order to preserve the efficacy and reduce toxic side effects, the “old medicine†was redeveloped to obtain a broad-spectrum antibacterial property. Self-assembled nanofibers that inhibit "granuloma" and scar formation - "phenytoin silver". The relevant research results were published in Theranostics in January 2017, and the paper titled "Phenytoin silver: a new nanocompound for promoting dermal wound healing via comprehensive pharmacological action".
Image source: Nankai University
"Phenytoin" is an ancient anti-epileptic and arrhythmogenic drug. Professor Yang Cheng from the School of Pharmacy of Nankai University used the effect of promoting wound healing to redevelop “old medicine†and obtained a self-assembled nanofiber with broad-spectrum antibacterial properties, inhibition of “granuloma†and scar formation. - "Phenytoin silver". The traumatic nano-medicine has good application prospects in many fields such as wound healing, diabetic foot, surgery, and war wound treatment.
In an accidental opportunity in World War II, "phenytoin" was used for war wound treatment. Subsequent studies have found that "phenytoin" has a good effect on wounds and skin ulcers caused by various causes. However, when it is used to treat trauma, it will strongly stimulate the wound and cause severe pain. The use of large-area wounds may also cause side effects such as lethargy. In addition, "phenytoin" does not have antibacterial activity, and the wound is prone to purulent infection.
Based on the above problems, researchers at Nankai University launched an optimized redevelopment of "phenytoin".
In response to wound irritation and infection, the researchers tried to add silver to the new drug. "Silver itself has a broad-spectrum antibacterial activity. The introduction of silver avoids wound irritation and does not confer a broad-spectrum antibacterial activity of 'phenytoinin silver' without affecting the 'phenytoin' promoting wound healing."
"At the same time, it was found that phenytoin silver can form nano-network under certain conditions and evenly cover the wound surface, which can promote wound healing and effectively prevent infection. Its effect is far more than that of phenytoin and silver."
The drug target of "phenytoin silver" is gp130 in the connective tissue near the wound, which promotes the growth of fibroblasts and the proliferation of epithelial cells, and achieves wound healing. This target is closely related to matrix remodeling, and can regulate the scar formation caused by excessive secretion of collagen by fibroblasts, thereby inhibiting scar formation.
The "phenytoin silver" nanomesh is much lower than the cell size, thus reducing the likelihood of "granuloma". At the same time, as a nano drug, its particle size is small and its specific surface area is high, so it has certain advantages over traditional molecular drugs, such as enhanced ability to pass through biofilm, high bioavailability, and low toxic side effects.
As a topical drug, "phenytoin silver" can be formulated into a dosage form such as an application or a film spray.
The development of “Phenytoin Silver†not only has indications, changes in preparations and modes of administration, but also redeveloped the “old medicine†compounds, which is more innovative and belongs to the “old medicine†redevelopment, with the goal of recent development. Apply for clinical approval.
"Re-development of old drugs" is of great significance for the development of new drugs. Due to the long-term clinical application of “old medicineâ€, there may be profound research on the possible problems. The new compounds obtained by limited modification and optimization may have excellent drug-forming properties, and the drug development can greatly save R&D cycle and cost.
Recently, this new drug, which was jointly researched by the Nankai University School of Pharmacy and the State Key Laboratory of Medicinal Chemistry Biology and the Tianjin International Biomedical Joint Research Institute, has applied for national invention patents and PCT, and entered the stage of fruit transformation. The paper introducing the results was published in the international journal Theranostics.
The following is an interview with Yan Tao on the team of Professor Yang Cheng.
When did you start this research?
Starting in 2013. We have been inspired by the pharmacological action of phenytoin to promote collagen synthesis in cells, and have been developed for four years.
What is the biggest highlight of this research?
The biggest bright spot is the realization of a drug that promotes wound healing and broad-spectrum antibacterial, overcoming the inconvenience and possible side effects of previous combination drugs.
The broad-spectrum antibacterial effect of silver is different from antibiotics, it is hardly sensitized, safe and effective. Combined with phenytoin, which promotes wound healing, this kind of safe and highly applicable traumatic drug is obtained. At the same time, we found that phenytoin silver can form nano-network under certain conditions, evenly covering the surface of the wound, and can prevent wound infection, which far exceeds the effect of phenytoin and silver.
Is the research result of phenytoin silver unexpected?
The research results of phenytoin silver are basically in line with research ideas and expectations, but the formation of nano-networks is unexpected. Because the formation of nano-networks is due to the fact that phenytoin silver is fibrous, and we expect it to be particles. But this feature has become a major advantage of the drug.
Have you encountered any difficulties during the research?
The nanocrystallization of phenytoin silver is difficult. We tried a lot of experimental conditions, and finally explored the ultrasonic synthesis method, and then obtained the nano-level fiber after specific separation.
How will you advance this research in the next step?
At present, our research on phenytoin silver is limited to its pharmacological effects, such as the molecular mechanism of its action, the effect of promoting wound healing and so on. With the completion of these tasks, we will gradually advance to the clinic to explore the optimal dosage form of phenytoin, so as to extend the duration of action while improving the efficacy and comfort of patients, and to lay down the final drug. basis.
Source: Nankai University
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