基于抗生素的小分子胶束结合光动力治疗细菌感染

IF 10.7 1区 医学 Q1 PHARMACOLOGY & PHARMACY Asian Journal of Pharmaceutical Sciences Pub Date : 2023-05-01 DOI:10.1016/j.ajps.2023.100810
Lijiao Yang , Shaomin Song , Meihui Yin , Min Yang, Daoping Yan, Xiaohui Wan, Jipeng Xiao, Yuchen Jiang, Yongchao Yao, Jianbin Luo
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引用次数: 1

摘要

耐多药细菌的出现和细菌生物膜的形成使得开发替代的抗菌疗法成为必要。与纳米药物载体偶联或包埋在纳米药物载体中的抗生素比游离药物显示出巨大的潜力和优势,但载体的质量比例通常超过纳米药物的90%,导致药物载量低,治疗效果有限。在此,我们使用抗生素作为构建块制造了纳米载体,最大限度地减少了载体材料的使用,显著提高了载药量和治疗效果。首先,我们通过酯键将甜菜碱羧酸盐与环丙沙星(CIP)偶联,形成两亲性偶联物(CIP-CB),该偶联物在水溶液中自组装成胶束(CIP-CBM),具有高达65.4%的CIP负载量和pH诱导的表面电荷反转特性。其次,将模型光敏剂(5,10,15,20四苯基卟啉(TPP))封装在CIP CBM中,产生感染靶向的光动力/抗生素组合纳米药物(表示为TPP@CIP-CBMs)。在感染部位或深层细菌生物膜中积累后,甜菜碱羧酸盐和CIP之间的酯键被裂解,释放出游离的TPP和CIP,从而在体外和体内产生协同的抗菌和抗生物膜活性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Antibiotic-based small molecular micelles combined with photodynamic therapy for bacterial infections

The appearance of multidrug-resistant bacteria and the formation of bacterial biofilms have necessitated the development of alternative antimicrobial therapeutics. Antibiotics conjugated with or embedded in nano-drug carriers show a great potential and advantage over free drugs, but the mass proportion of carriers generally exceeds 90% of the nano-drug, resulting in low drug loading and limited therapeutic output. Herein, we fabricated a nanocarrier using antibiotics as the building blocks, minimizing the use of carrier materials, significantly increasing the drug loading content and treatment effect. Firstly, we conjugated betaine carboxylate with ciprofloxacin (CIP) through an ester bond to form the amphiphilic conjugate (CIP-CB), which self-assembled into micelles (CIP-CBMs) in aqueous solutions, with a CIP loading content as high as 65.4% and pH-induced surface charge reversal properties. Secondly, a model photosensitizer (5, 10, 15, 20-tetraphenylporphyrin (TPP)) was encapsulated in CIP-CBMs, generating infection-targeted photodynamic/antibiotic combined nanomedicines (denoted as TPP@CIP-CBMs). Upon accumulation at infection sites or in deep bacterial biofilms, the ester bond between the betaine carboxylate and CIP is cleaved to release free TPP and CIP, leading to a synergetic antibacterial and antibiofilm activity in vitro and in vivo.

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来源期刊
Asian Journal of Pharmaceutical Sciences
Asian Journal of Pharmaceutical Sciences Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
18.30
自引率
2.90%
发文量
11
审稿时长
14 days
期刊介绍: The Asian Journal of Pharmaceutical Sciences (AJPS) serves as the official journal of the Asian Federation for Pharmaceutical Sciences (AFPS). Recognized by the Science Citation Index Expanded (SCIE), AJPS offers a platform for the reporting of advancements, production methodologies, technologies, initiatives, and the practical application of scientific knowledge in the field of pharmaceutics. The journal covers a wide range of topics including but not limited to controlled drug release systems, drug targeting, physical pharmacy, pharmacodynamics, pharmacokinetics, pharmacogenomics, biopharmaceutics, drug and prodrug design, pharmaceutical analysis, drug stability, quality control, pharmaceutical engineering, and material sciences.
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