Faculty of Biological Science and Technology, Department of Cellular and Molecular Biology and Microbiology, University of Isfahan, Isfahan, Iran.
Faculty of Biological Science and Technology, Department of Biotechnology, Shahid Ashrafi Esfahani University, Isfahan, Iran.
Appl Biochem Biotechnol. 2023 Jun;195(6):3733-3746. doi: 10.1007/s12010-022-04068-3. Epub 2022 Jul 27.
Lipopeptides have been the subject of great interest as vehicles for drug delivery, but the potential usage of their biological composites has not been extensively studied. Here, the extracellular lipopeptide composite (ELC) of a lipopeptide-producing bacterium was extracted and examined to deliver doxorubicin (DOX) as a cationic drug. MALDI-TOF mass spectrometry analysis on the lipopeptide moiety of ELC revealed that this hydrogel consists of 13 lipopeptide isomers. Furthermore, scanning electron microscope (SEM) studies showed that the permeability of ELC in acidic pH was significantly more than basic condition. In this study, 81% of DOX was successfully entrapped in ELC and the release of the drug was measured in acidic, neutral, and basic conditions. The results indicated that the release profile of the drug in acidic pH was about 10 and 16 fold more than neutral and basic conditions, respectively. Besides, the toxicity of DOX-conjugated ELC against PBMC cells was more than free DOX, suggesting the adequate drug release from ELC. Since the surrounding environment of tumor cells is often acidic, this pH-sensitive carrier could be a candidate for cancer therapy to improve the exposure of tumor cells to the drugs.
脂肽一直是药物输送载体的研究热点，但它们的生物复合材料的潜在用途尚未得到广泛研究。在这里，从产生脂肽的细菌中提取并研究了细胞外脂肽复合物（ELC），以作为阳离子药物递送来输送阿霉素（DOX）。ELC 中脂肽部分的 MALDI-TOF 质谱分析表明，这种水凝胶由 13 种脂肽异构体组成。此外，扫描电子显微镜（SEM）研究表明，ELC 在酸性 pH 下的通透性明显高于碱性条件。在这项研究中，81%的 DOX 成功地被包封在 ELC 中，并在酸性、中性和碱性条件下测量了药物的释放。结果表明，药物在酸性 pH 下的释放模式比中性和碱性条件下分别高出约 10 倍和 16 倍。此外，与游离 DOX 相比，与 DOX 缀合的 ELC 对 PBMC 细胞的毒性更大，这表明 ELC 能够充分释放药物。由于肿瘤细胞周围的环境通常是酸性的，这种 pH 敏感的载体可以作为癌症治疗的候选药物，以提高肿瘤细胞对药物的暴露程度。
