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Liposome-Based Delivery of Therapeutic Agents
Published in Emmanuel Opara, Controlled Drug Delivery Systems, 2020
Eneida de Paula, Juliana Damasceno Oliveira, Fernando Freitas de Lima, Lígia Nunes de Morais Ribeiro
The broadest spectrum agents of antifungal therapy worldwide in the last 50 years have been the polyene compounds (e.g. amphotericin, nystatin, hamycin, dermostatin, etc.). Amphotericin B (AMB) is the gold standard antifungal drug, but its use is still associated with severe adverse effects (mainly impairment of nephron function by cumulative doses, besides fever, chills, myalgia, and thrombophlebitis), low clinical response, and high mortality rates. Another class of antifungal, the azoles, include ketoconazole, fluconazole, and itraconazole (launched in the 80s), and later the second-generation triazoles voriconazole, ravuconazole, and posaconazole. Their good activity against molds brought some help to the antifungal therapy, although some of them are mostly used as topical agents. Allylamines, such as butenafine and naftifine, are the third class of antimycotic agents that are able to inhibit squalene epoxidase, restraining the synthesis of ergosterol.143 In the beginning of the 21st century, another class of drugs, the echinocandins–noncompetitive inhibitors of β-1-3-glucan synthase, blocking the synthesis of the fungal cell wall – appeared as a promise for the candidiasis and aspergillosis treatment.144,145
Novel Microbial Compounds as a Boon in Health Management
Published in Jyoti Ranjan Rout, Rout George Kerry, Abinash Dutta, Biotechnological Advances for Microbiology, Molecular Biology, and Nanotechnology, 2022
Shubha Rani Sharma, Rajani Sharma, Debasish Kar
Fungal cell wall mainly contains glucan, chitin, and mannoproteins. Glucan is the polymer of glucose. The monomer units of glucose are linked by (1–3)-β or (1,6)-β bonds. Echinocandins inhibit noncompetitively β-1,3-glucan synthase and disrupt the cell wall formation in fungus (Emri et al., 2013). Pneumocandins that belong to the echinocandins family also show a similar mechanism of inhibitory action on the growth of fungus (Chen et al., 2015). Chitin is also a polysaccharide made of β-(1,4)-linked N-acetylglucosamine monomers. Secondary metabolites belonging to a peptide-nucleoside family, which are similar to UDP-N-acetylglucosamine, inhibit competitively chitin synthesis. Few of the antifungal compounds have been noted in Table 5.9.
Pulmonary complications of solid-organ transplantation
Published in Philippe Camus, Edward C Rosenow, Drug-induced and Iatrogenic Respiratory Disease, 2010
Amphotericin B has traditionally been the mainstay of therapy for invasive aspergillosis but its many side-effects and need for intravenous administration have made it a rather unappealing choice. More recently, liposomal amphotericin preparations have been introduced that are less nephrotoxic than the parent compound, an important feature for a drug used concurrently with calcineurin inhibitors (ciclosporin, tacrolimus). The triazoles itraconazole and voriconazole offer the advantages of availability in both oral and intravenous formulations and absence of nephrotoxicity. Voriconazole absorption from the gastrointestinal tract is much more reliable than that of itraconazole, making it the preferred oral agent. Voriconazole recently was shown to have superior efficacy and less toxicity than amphotericin B in the treatment of invasive asperillosis, and it is emerging as first-line therapy in many centres.32 Both of the triazoles are potent inhibitors of the P450 hepatic enzyme system and can lead to dangerously high blood levels of ciclosporin and tacrolimus if appropriate adjustments in the dosing of these agents are not made. Because of particularly profound interactions, the concurrent use of voriconazole and sirolimus is contraindicated. Caspofungin, the first of a new class of echinocandins, has been approved in the United States for treatment of invasive aspergillosis in patients who fail or are intolerant of first-line therapy. Despite the availability of antifungal therapy, mortality is in the range of 30–90 per cent, with the highest mortality rates associated with disseminated disease. The therapeutic role of surgical resection remains uncertain but surgery has been advocated in cases of localized infection refractory to medical therapy.33
Mutagenesis of echinocandin B overproducing Aspergillus nidulans capable of using starch as main carbon source
Published in Preparative Biochemistry & Biotechnology, 2020
Zhong-Ce Hu, Wen-Jun Li, Shu-Ping Zou, Kun Niu, Yu-Guo Zheng
Echinocandins, a class of cyclic hexlipopeptides antibiotic, have strong antifungal activity to noncompetitive inhibit the activity of 1,3-β-d-glucan synthase, resulting in abnormal biosynthesis of fungal cell walls.[1,2] Echinocandin B has unique pharmacological properties, less toxic and broad-spectrum antifungal activity.[3,4] Many reports are available on echinocandin B fermentation.[3,5–7] One of the most urgent problems in echinocandin B fermentation is the relatively high cost of fermentation medium. Among the total cost of fermentation medium, carbon sources account for 60-70%. Mannitol had been reported as the optimal carbon source in echinocandin B fermentation, but it is uneconomic compared with glucose, sucrose, and starch. Selection of cheap carbon source, usage of overproducing mutant, and bioprocess optimization were the main strategies for reduction of cost.[6,8] A great deal of effort has been focused on echinocandin B fermentation in our laboratory.[6,7] A combined mutagenesis of UV radiation and microwave radiation treatment has been developed to screen mutant capable of using cheap carbon source for echinocandin B fermentation. A stable high-yield mutant ZJB12073 using fructose as carbon source instead of mannitol had been obtained.[6] Although fructose is much cheaper than mannitol, it is still an expensive carbon source in fermentation industry. As we know, starch is a kind of cheap carbon source, and has been used widely in antibiotic fermentation. Selecting a mutant of A. nidulans which can use starch as main carbon source was one of the promising ways to reduce the cost of fermentation medium for echinocandin B production. In this work, atmospheric and room temperature plasma (ARTP) was applied to select mutants capable of using cheap starch as main carbon source instead of expensive fructose.