Chelating Complex Micelles for Delivering Cytoprotectant Amifostine and its Application in Radiation Protection

Wang, Chau Hui; Cheng, Chia Yi; Chen, Chia-Hung; Liao, Wei Chuan; Lin, Johnson

doi:10.4172/2329-6887.1000263

Cited by 1 publication

(1 citation statement)

References 21 publications

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“…In contrast, PEG has been widely used in drug carriers and approved for clinical trials [18,19]. Thus, CCMs have extended the half-life and antiradiation efficacy of amifostine, an old drug, and have received approval from the U.S. Food and Drug Administration for a phase I clinical trial [20][21][22]. This indicates that CCMs reach the safety requirements necessary for research.…”

Section: Introductionmentioning

confidence: 99%

The Antimicrobial Effects of Colistin Encapsulated in Chelating Complex Micelles for the Treatment of Multi-Drug-Resistant Gram-Negative Bacteria: A Pharmacokinetic Study

Liao

Wang²,

Sun

et al. 2023

Antibiotics

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Background: Infections caused by multi-drug-resistant Gram-negative bacteria (MDR-GNB) are an emerging problem globally. Colistin is the last-sort antibiotic for MDR-GNB, but its toxicity limits its clinical use. We aimed to test the efficacy of colistin-loaded micelles (CCM-CL) against drug-resistant Pseudomonas aeruginosa and compare their safety with that of free colistin in vitro and in vivo. Materials and methods: We incorporated colistin into chelating complex micelles (CCMs), thus producing colistin-loaded micelles (CCM-CL), and conducted both safety and efficacy surveys to elucidate their potential uses. Results: In a murine model, the safe dose of CCM-CL was 62.5%, which is much better than that achieved after the intravenous bolus injection of ‘free’ colistin. With a slow drug infusion, the safe dose of CCM-CL reached 16 mg/kg, which is double the free colistin, 8 mg/kg. The area under the curve (AUC) levels for CCM-CL were 4.09- and 4.95-fold higher than those for free colistin in terms of AUC0-t and AUC0-inf, respectively. The elimination half-lives of CCM-CL and free colistin groups were 12.46 and 102.23 min, respectively. In the neutropenic mice model with carbapenem-resistant Pseudomonas aeruginosa pneumonia, the 14-day survival rate of the mice treated with CCM-CL was 80%, which was significantly higher than the 30% in the free colistin group (p < 0.05). Conclusions: Our results showed that CCM-CL, an encapsulated form of colistin, is safe and effective, and thus may become a drug of choice against MDR-GNB.

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