Reducing the toxicity of amphotericin B by encapsulation using methoxy poly(ethylene glycol)-b-poly(l-glutamic acid-co-l-phenylalanine),Biomaterials Science

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Reducing the toxicity of amphotericin B by encapsulation using methoxy poly(ethylene glycol)-b-poly(l-glutamic acid-co-l-phenylalanine)
Biomaterials Science ( IF 5.8 ) Pub Date : 2018-06-27 00:00:00 , DOI: 10.1039/c8bm00506k
Chenguang Yang _{1,

2,

3,

4,

5} , Baiji Xue _{5,

6,

7,

8} , Wantong Song _{1,

2,

3,

4,

5} , Bo Kan _{4,

5,

9} , Dawei Zhang _{1,

2,

3,

4,

5} , Haiyang Yu _{1,

2,

3,

4,

5} , Na Shen _{1,

2,

3,

4,

5} , Xuefeng Li _{5,

6,

7,

8} , Zhaohui Tang _{1,

2,

3,

4,

5} , Xuesi Chen _{1,

2,

3,

4,

5}

Affiliation

Amphotericin B (AmB) is an antifungal drug used for serious fungal infections and leishmaniosis. However, its clinical application is limited because of its high toxicity. To resolve this problem, herein we loaded AmB into methoxy poly(ethylene glycol)-b-poly(L-glutamic acid-co-L-phenylalanine) (mPEG-b-P(Glu-co-Phe)) nanoparticles (L-AmB) via electrostatic, hydrophobic and π–π interactions. The L-AmB has excellent stability both in PBS and in plasma and shows a remarkably reduced hemolysis (17.1 ± 1.5%, 6 h) compared to the free AmB (94.2 ± 5.3%, 6 h). The nephrotoxicity of L-AmB is significantly lower than that of free AmB. The maximum tolerance dose (MTD) of L-AmB is 3.0 mg kg⁻¹, which is 3.75 fold that of free AmB (MTD = 0.8 mg kg⁻¹). The antimicrobial activity of the conjugate was retained in vivo, with L-AmB proving to be a more protective treatment for Aspergillus fumigatus infections in mice than AmB alone. These indicate that L-AmB is a formulation of AmB with low side effects.

中文翻译：

使用甲氧基聚（乙二醇）通过封装减少两性霉素B的毒性- b -聚（升-谷氨酸酸共-升-苯丙氨酸）

两性霉素B（AmB）是一种用于严重真菌感染和利什曼病的抗真菌药。然而，由于其高毒性，其临床应用受到限制。要解决此问题，在此我们加载到霉素甲氧基聚（乙二醇） - b -聚（大号-谷氨酸酸共-大号-苯丙氨酸）（的mPEG- b -P（Glu-共-Phe））纳米颗粒（大号- AmB）通过静电，疏水和π–π相互作用。的大号-AmB同时具有在PBS中并在等离子体和显示出优异的稳定性相比，游离两性霉素B（94.2±5.3％，6小时）一个显着降低溶血（17.1±1.5％，6小时）。L的肾毒性-AmB明显低于免费的AmB。L -AmB的最大耐受剂量（MTD）为3.0 mg kg ^-1，是游离AmB（MTD = 0.8 mg kg ^-1）的3.75倍。结合物的抗菌活性在体内得以保留，与单独使用AmB相比，L- AmB被证明对小鼠烟曲霉感染更具保护性。这些表明L -AmB是具有低副作用的AmB的制剂。

更新日期：2018-06-27

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