Multifunctional Dual Enzyme-Responsive Nanostructured Lipid Carriers for Targeting and Enhancing the Treatment of Bacterial Infections.

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS
ACS Applied Bio Materials Pub Date : 2025-01-20 Epub Date: 2024-12-23 DOI:10.1021/acsabm.4c01436
Kerisha Chetty, Xylia Q Peters, Calvin A Omolo, Eman A Ismail, Mohammed A Gafar, Eman Elhassan, Sania Z F Kassam, Jasoda Govender, Sbongumusa Dlamini, Thirumala Govender
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引用次数: 0

Abstract

Bacterial infections pose an increasingly worrisome threat to the health of humankind, with antibiotic resistance contributing significantly to this burden. With current conventional antibiotics perpetuating the problem, and a paucity in developing antibiotics, drug delivery systems incorporating nanotechnology appear promising. As such, a dual enzyme-responsive multifunctional nanostructured lipid carrier (NLC) incorporating farnesol (FAN) and triglycerol monostearate (TGMS), was conceptualized for the codelivery of vancomycin (VCM) and antimicrobial peptide (AMP) to enhance the antibacterial activity of VCM. In silico studies and Microscale Thermophoresis demonstrated the strong binding relationships between the NLC constituents and two enzymes that exist in higher concentrations during host infection, namely lipase and a matrix metalloproteinase (MMP). The formulated nanosystem, VCM-AMP-TF-NLCs, had a particle size, polydispersity index, zeta potential, and entrapment efficiency of 149.00 ± 2.97 nm, 0.07 ± 0.01, -5.51 ± 1.21 mV, and 86.20% ± 1.47%, respectively. The NLCs, which showed stability, and biocompatibility, also demonstrated lipase- and MMP-responsiveness. The in vitro antibacterial studies revealed 2-fold and 8-fold reductions in the minimum inhibitory concentration for the NLCs compared to bare VCM, against methicillin-resistant Staphylococcal aureus (MRSA) and Escherichia coli, respectively. Furthermore, in vivo studies revealed that tissues treated with the VCM-AMP-TF-NLCs displayed significantly reduced bacterial burdens (up to 8.73-fold) and less histopathological cellular injury, edema, and necrosis compared to the tissues treated with bare VCM alone. The results support the superiority of the VCM-AMP-TF-NLCs as a multifunctional dual enzyme-responsive NLC compared to bare VCM.

靶向和增强细菌感染治疗的多功能双酶反应纳米结构脂质载体。
细菌感染对人类健康构成日益令人担忧的威胁,抗生素耐药性在很大程度上加剧了这一负担。由于目前的传统抗生素使这个问题长期存在,而且开发抗生素方面的匮乏,结合纳米技术的药物输送系统似乎很有希望。因此,一种含有法尼醇(FAN)和甘油三酯单硬脂酸酯(TGMS)的双酶反应多功能纳米结构脂质载体(NLC)被概念化,用于万古霉素(VCM)和抗菌肽(AMP)的共递送,以增强VCM的抗菌活性。计算机研究和微尺度热电泳表明,NLC成分与宿主感染期间存在的两种较高浓度的酶,即脂肪酶和基质金属蛋白酶(MMP)之间存在很强的结合关系。制备的纳米体系vcm - amp - tf - nlc的粒径为149.00±2.97 nm,多分散性指数为0.07±0.01,zeta电位为-5.51±1.21 mV,包封效率为86.20%±1.47%。NLCs表现出稳定性和生物相容性,也表现出脂肪酶和mmp的反应性。体外抗菌研究显示,与裸VCM相比,NLCs对耐甲氧西林金黄色葡萄球菌(MRSA)和大肠杆菌的最低抑菌浓度分别降低了2倍和8倍。此外,体内研究显示,与单独使用VCM处理的组织相比,用VCM- amp - tf - nnlcs处理的组织显示出明显减少的细菌负担(高达8.73倍),组织病理学细胞损伤,水肿和坏死较少。结果表明,与裸VCM相比,VCM- amp - tf -NLC作为多功能双酶反应NLC具有优势。
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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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
期刊介绍: ACS Applied Bio Materials is an interdisciplinary journal publishing original research covering all aspects of biomaterials and biointerfaces including and beyond the traditional biosensing, biomedical and therapeutic applications. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrates knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important bio applications. The journal is specifically interested in work that addresses the relationship between structure and function and assesses the stability and degradation of materials under relevant environmental and biological conditions.
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