Erythromycin Formulations—A Journey to Advanced Drug Delivery

Platon, Vera-Maria; Drăgoi, Brînduşa; Marin, Luminița

doi:10.3390/pharmaceutics14102180

Cited by 19 publications

(3 citation statements)

References 165 publications

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“…Their wide habitat range and interactions with diverse organisms led to the evolution of intricate natural product biosynthesis, captivating the drug discovery field [4]. Commercially, Actinobacteria have contributed an impressive array of natural product based drugs, including immunosuppressants like ascomycin and rapamycin [5,6], antibiotics such as erythromycin and tetracycline [7,8], and other compounds with applications spanning antifungal, antiviral, immunostimulant, anti-cancer, and agriculturally valuable properties [9,10].…”

Section: Introductionmentioning

confidence: 99%

Discovery, characterization, and engineering of an advantageous Streptomyces host for heterologous expression of natural product biosynthetic gene clusters

Klumbys,

Xu,

Koduru

et al. 2024

Microb Cell Fact

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Background Streptomyces is renowned for its robust biosynthetic capacity in producing medically relevant natural products. However, the majority of natural products biosynthetic gene clusters (BGCs) either yield low amounts of natural products or remain cryptic under standard laboratory conditions. Various heterologous production hosts have been engineered to address these challenges, and yet the successful activation of BGCs has still been limited. In our search for a valuable addition to the heterologous host panel, we identified the strain Streptomyces sp. A4420, which exhibited rapid initial growth and a high metabolic capacity, prompting further exploration of its potential. Results We engineered a polyketide-focused chassis strain based on Streptomyces sp. A4420 (CH strain) by deleting 9 native polyketide BGCs. The resulting metabolically simplified organism exhibited consistent sporulation and growth, surpassing the performance of most existing Streptomyces based chassis strains in standard liquid growth media. Four distinct polyketide BGCs were chosen and expressed in various heterologous hosts, including the Streptomyces sp. A4420 wild-type and CH strains, alongside Streptomyces coelicolor M1152, Streptomyces lividans TK24, Streptomyces albus J1074, and Streptomyces venezuelae NRRL B-65442. Remarkably, only the Streptomyces sp. A4420 CH strain demonstrated the capability to produce all metabolites under every condition outperforming its parental strain and other tested organisms. To enhance visualization and comparison of the tested strains, we developed a matrix-like analysis involving 15 parameters. This comprehensive analysis unequivocally illustrated the significant potential of the new strain to become a popular heterologous host. Conclusion Our engineered Streptomyces sp. A4420 CH strain exhibits promising attributes for the heterologous expression of natural products with a focus on polyketides, offering an alternative choice in the arsenal of heterologous production strains. As genomics and cloning strategies progress, establishment of a diverse panel of heterologous production hosts will be crucial for expediting the discovery and production of medically relevant natural products derived from Streptomyces.

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Section: Introductionmentioning

confidence: 99%

Discovery, characterization, and engineering of an advantageous Streptomyces host for heterologous expression of natural product biosynthetic gene clusters

Klumbys,

Xu,

Koduru

et al. 2024

Microb Cell Fact

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“….) have been studied, but none is yet commercialized [21]. In current pediatric practice, hospital pharmacists' choices are often limited to liquid oral form (suspension) or dry oral form (capsules).…”

Section: Introductionmentioning

confidence: 99%

Low-dose erythromycin in pediatrics: Formulation and stability of 20 mg hard gelatin capsules

Thevin¹,

Curti²,

Benech³

et al. 2023

PLoS ONE

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Objective Erythromycin is a macrolide antibiotic that is also prescribed off-label in premature neonates as a prokinetic agent. There is no oral formulation with dosage and/or excipients adapted for these high-risk patients. Methods Clinical studies of erythromycin as a prokinetic agent were reviewed. Capsules of 20 milligrams of erythromycin were compounded with microcrystalline cellulose. Erythromycin capsules were analyzed using the chromatographic method described in the United States Pharmacopoeia which was found to be stability-indicating. The stability of 20 mg erythromycin capsules stored protected from light at room temperature was studied for one year. Results 20 mg erythromycin capsules have a beyond use date not lower than one year. Conclusion 20 milligrams erythromycin capsules can be compounded in batches of 300 unities in hospital pharmacy with a beyond-use-date of one year at ambient temperature protected from light.

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“…With the widespread use of traditional antibiotics, the resistance of bacteria has gradually increased, resulting in considerably resistant bacteria and the emergence of multidrug resistant (MDR) strains, even super bacteria (da Silva et al, 2022;Zhou et al, 2022). However, the resistance rate of old-fashioned antibacterial drugs such as penicillin, cephalosporin, erythromycin, and azithromycin has even reached 80%-90% (Tan et al, 2018;Murray et al, 2022;Platon et al, 2022;She et al, 2022). Meanwhile, new antibacterial drugs have not been successfully developed.…”

Section: Introduction 1backgroundmentioning

confidence: 99%

A natural product noraucupatin against multidrug-resistant Enterococcus faecium: an inhibition mechanism study

et al. 2023

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Background: This work elucidates the antimicrobial activity and mechanism of action of the natural product noraucupatin against MDR Enterococcus faecium. E. faecium has become a major opportunistic pathogen with the worldwide spread of multidrug-resistant (MDR) isolates, especially vancomycin-resistant enterococci (VRE), belongs to “ESKAPE” organisms causing significant problems widely. Hence, there is a pressing need to discover new promising drugs or alternative therapies. Fortunately, we found a natural product noraucupatin (C13H12O3, a biphenyl compound) with “extremely encouraging” anti-clinical drug-resistant bacterial activity isolated from yeast-induced Rowan suspension cells. A comprehensive and in-depth exploration of antimicrobial mechanisms will bring fresh insights for researchers to develop novel antimicrobial strategies against MDR bacteria.Methods: The antibacterial effect of noraucupatin against MDR E. faecium is investigated from a microbial metabolism perspective using microcalorimetry. The antibacterial effect is determined based on the thermodynamic parameters. Based on spectroscopic techniques, microscopy techniques and confocal scanning laser microscopy with membrane probes, the antibacterial mechanism is elucidated definitely.Results: Comparing with the IC50 of noraucupatin against MDR Enterococcus faecalis, MRSA, CRPA, the IC50 of noraucupatin against MDR E. faecium was just 67.54 μM. The growth rate of MDR E. faecium decreases with the increase of concentration of noraucupatin. The bacterial intracellular structure entirely collapses and the slurries flow out under the influence of high levels of noraucupatin by TEM. The changes of membrane potential, permeability and evidences of nucleic acid leakage was obtained by CSLM and UV, the mechanism of noraucupatin against MDR E. faecium we explored.Conclusion: The present study highlights the excellent antibacterial activity of noraucupatin against MDR E. faecium by altering the permeability of the membrane and disrupting the membrane potential leading to electrolyte permeation. In addition, noraucupatin has excellent biocompatibility through its haemolytic activity in rabbit erythrocyte. These findings suggest that noraucupatin could be used in infectious diseases caused by MDR E. faecium.

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Erythromycin Formulations—A Journey to Advanced Drug Delivery

Cited by 19 publications

References 165 publications

Discovery, characterization, and engineering of an advantageous Streptomyces host for heterologous expression of natural product biosynthetic gene clusters

Discovery, characterization, and engineering of an advantageous Streptomyces host for heterologous expression of natural product biosynthetic gene clusters

Low-dose erythromycin in pediatrics: Formulation and stability of 20 mg hard gelatin capsules

A natural product noraucupatin against multidrug-resistant Enterococcus faecium: an inhibition mechanism study

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