Yongfeng Zhao,Ying Fan,Yan Zhang,Hong Xu,Min Li,Yunjie Zhu,Zhao Yang
According to crystal engineering, the pharmaceutical intermediate m -nitrobenzoic acid (MNBA), which contains a carboxylic acid group, was selected as a coformer (CCF) for drug cocrystallization with famotidine (FMT), and a new stable FMT salt cocrystal was synthesized. The salt cocrystals were characterized by scanning electron microscopy, differential scanning calorimetry, thermogravimetric analysis, infrared spectroscopy, powder X-ray diffraction and X-ray single crystal diffraction. A single crystal structure of FMT–MNBA (1:1) was successfully obtained, and then the solubility and permeability of the newly synthesized salt cocrystal were studied. The results showed that, compared with free FMT, the FMT from the FMT–MNBA cocrystal showed improved permeability. This study provides a synthetic method to improve the permeability of BCS III drugs, which will contribute to the development of low-permeability drugs.
Meng-na Zhang,Xiao-ou Zhao,Qi Cui,Dao-mi Zhu,Muhammad Asif Wisal,Han-dong Yu,Ling-cong Kong,Hong-xia Ma
The development of novel antibiotic adjuvants is imminent because of the frequent emergence of resistance in Gram-negative bacteria, which severely restricts the efficiency and longevity of commonly used clinical antibiotics. It is reported that famotidine, a clinical inhibitor of gastric acid secretion, enhances the antibacterial activity of rifamycin antibiotics, especially rifampicin, against Gram-negative bacteria and reverses drug resistance. Studies have shown that famotidine disrupts the cell membrane of Acinetobacter baumannii and inhibits the expression of the outer membrane protein ompA gene, while causing a dissipation of the plasma membrane potential, compensatively upregulating the pH gradient and ultimately increasing the accumulation of reactive oxygen species by leading to increased bacterial mortality. In addition, famotidine also inhibited the efflux pump activity and the biofilm formation of A. baumannii. In the Galleria mellonella and mouse infection models, the combination of famotidine and rifampicin increased the survival rate of infected animals and decreased the bacterial load in mouse organs. In conclusion, famotidine has the potential to be a novel rifampicin adjuvant, providing a new option for the treatment of clinical Gram-negative bacterial infections.IMPORTANCE In this study, famotidine was discovered for the first time to have potential as an antibiotic adjuvant, enhancing the antibacterial activity of rifamycin antibiotics against A. baumannii and overcoming the limitations of drug therapy. With the discovery of novel applications for the guanidine-containing medication famotidine, the viability of screening prospective antibiotic adjuvants from guanidine-based molecules was further explored. In addition, famotidine exerts activity by affecting the OmpA protein of the cell membrane, indicating that this protein might be used as a therapeutic drug target to treat A. baumannii infections.
Enwereuzo Onyekachi Oluchi,Akakuru Obinna Chigoziem,Uwaoma Romanus Chinonso,Elemike Elias Emeka,Akakuru Ozioma Udochukwu
Controlled release technology has continuously attracted attention as a strategy to deliver active agents to specific internal body regions with attendant cost-effectiveness among other intriguing merits. Here, drug-loaded nanoparticles (NPs) are synthesized for ultimate application in the treatment of gastroesophageal reflux disease (GERD), leveraging the benefits of controlled release strategy. To achieve this, eggshell membranes (ESMs) were extracted and combined with chitosan (CHS) to rationally obtain self-assembled CHS–ESM NPs that served as a novel nanocarrier to effectively compartmentalize a GERD-therapeutic drug famotidine (FTD) and form self-assembled FTD@CHS–ESM NPs. Advantageously, the proof-of-concept FTD@CHS–ESM NPs offer superlative tissue tolerance. The cumulative FTD release is 89% after 12 h at pH 1.2, suggesting the capability of FTD@CHS–ESM NPs for effectual controlled drug release; a testimonial of the effective compartmentalization of FTD in the nanocarrier. Furthermore, the release of FTD from the FTD@CHS–ESM NPs is best described by Higuchi square root model, in a non-Fickian diffusional release mechanism ( n = 0.584 and 0.582 in pH 1.2 and pH 6.8, respectively). The drug release system demonstrated in this work, therefore, holds strong promise for the oral nanomedical treatment of GERD in vivo, and promotes the rational synthesis of organic-based biocompatible nanomaterials for biomedical application. Graphic abstract
危险品化学品经营许可证（带存储）