Sanat Kumar Dash, Derajram Benival and Anil B. Jindal*,
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AmB exerts its therapeutic activity at the cellular level by binding to fungal sterol and forming hydrophilic pores, releasing essential cellular components and ions into the extracellular fluid, leading to cell death. Despite using AmB as an antifungal and antileishmanial at a broad scale, its clinical use is limited due to drug-induced nephrotoxicity resulting from binding the aggregated form of the drug to mammalian sterol. To mitigate AmB-induced toxicity and to get better anti-fungal therapeutic outcomes, researchers have developed nanoformulations, self-assembled formulations, prodrugs, cholesterol- and albumin-based AmB formulations, AmB-mAb combination therapy, and AmB cochleates. These formulations have helped to reduce toxicity to a certain extent by controlling the aggregation state of AmB, providing sustained drug release, and altering the physicochemical and pharmacokinetic parameters of AmB. Although the preclinical outcome of AmB formulations is quite satisfactory, its parallel result at the clinical level is insignificant. However, the safety and efficacy of AmB therapy can be improved at the clinical stage by continuous investigation and collaboration among researchers, clinicians, and pharmaceutical companies.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"21 11","pages":"5392–5412 5392–5412"},"PeriodicalIF":4.5000,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Formulation Strategies to Overcome Amphotericin B Induced Toxicity\",\"authors\":\"Sanat Kumar Dash, Derajram Benival and Anil B. 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引用次数: 0
摘要
真菌感染因其广泛的流行性、严重的死亡率、诊断和治疗方面的挑战以及耐药真菌菌株的出现,对全球公共卫生构成了重大威胁。根据最新报告,数百万人受到真菌感染的影响,每年约有 380 万人死于真菌感染。自 1960 年以来,多烯类抗生素 AmB 已被广泛用作治疗全身真菌感染和利什曼病的药物。AmB 具有广谱杀真菌和杀真菌活性。AmB 通过与真菌固醇结合并形成亲水孔,在细胞水平发挥治疗活性,将细胞的基本成分和离子释放到细胞外液中,导致细胞死亡。尽管 AmB 被广泛用作抗真菌和抗利什曼病药物,但由于该药物的聚集形式与哺乳动物固醇结合会导致药物诱发肾毒性,因此其临床应用受到了限制。为了减轻 AmB 引起的毒性并获得更好的抗真菌治疗效果,研究人员开发了纳米制剂、自组装制剂、原药、基于胆固醇和白蛋白的 AmB 制剂、AmB-mAb 联合疗法和 AmB 辅酶。这些制剂通过控制 AmB 的聚集状态、持续释放药物以及改变 AmB 的理化和药代动力学参数,在一定程度上降低了其毒性。尽管 AmB 制剂的临床前研究结果相当令人满意,但其在临床上的平行结果并不显著。不过,通过研究人员、临床医生和制药公司之间的不断研究和合作,AmB 疗法的安全性和有效性在临床阶段可以得到改善。
Formulation Strategies to Overcome Amphotericin B Induced Toxicity
Fungal infection poses a major global threat to public health because of its wide prevalence, severe mortality rate, challenges involved in diagnosis and treatment, and the emergence of drug-resistant fungal strains. Millions of people are getting affected by fungal infection, and around 3.8 million people face death per year due to fungal infection, as per the latest report. The polyene antibiotic AmB has an extensive record of use as a therapeutic moiety against systemic fungal infection and leishmaniasis since 1960. AmB has broad-spectrum fungistatic and fungicidal activity. AmB exerts its therapeutic activity at the cellular level by binding to fungal sterol and forming hydrophilic pores, releasing essential cellular components and ions into the extracellular fluid, leading to cell death. Despite using AmB as an antifungal and antileishmanial at a broad scale, its clinical use is limited due to drug-induced nephrotoxicity resulting from binding the aggregated form of the drug to mammalian sterol. To mitigate AmB-induced toxicity and to get better anti-fungal therapeutic outcomes, researchers have developed nanoformulations, self-assembled formulations, prodrugs, cholesterol- and albumin-based AmB formulations, AmB-mAb combination therapy, and AmB cochleates. These formulations have helped to reduce toxicity to a certain extent by controlling the aggregation state of AmB, providing sustained drug release, and altering the physicochemical and pharmacokinetic parameters of AmB. Although the preclinical outcome of AmB formulations is quite satisfactory, its parallel result at the clinical level is insignificant. However, the safety and efficacy of AmB therapy can be improved at the clinical stage by continuous investigation and collaboration among researchers, clinicians, and pharmaceutical companies.
期刊介绍:
Molecular Pharmaceutics publishes the results of original research that contributes significantly to the molecular mechanistic understanding of drug delivery and drug delivery systems. The journal encourages contributions describing research at the interface of drug discovery and drug development.
Scientific areas within the scope of the journal include physical and pharmaceutical chemistry, biochemistry and biophysics, molecular and cellular biology, and polymer and materials science as they relate to drug and drug delivery system efficacy. Mechanistic Drug Delivery and Drug Targeting research on modulating activity and efficacy of a drug or drug product is within the scope of Molecular Pharmaceutics. Theoretical and experimental peer-reviewed research articles, communications, reviews, and perspectives are welcomed.