Synthesis of pH-responsive dimethylglycine surface-modified branched lipids for targeted delivery of antibiotics

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Chemistry and Physics of Lipids Pub Date : 2022-11-01 DOI:10.1016/j.chemphyslip.2022.105241

Sifiso S. Makhathini , Calvin A. Omolo , Lucy W. Kiruri , Pavan Walvekar , Nikita Devnarain , Chunderika Mocktar , Thirumala Govender

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引用次数: 1

Abstract

The rampant antimicrobial resistance crisis calls for efficient and targeted drug delivery of antibiotics at the infectious site. Hence, this study aimed to synthesize a pH-responsive dimethylglycine surface-modified branched lipid (DMGSAD-lipid). The structure of the synthesized lipid was fully confirmed. The lipid polymer hybrid nanoparticles (LPHNPs) were formulated using the solvent evaporation method and characterised. Two LPHNPs (VCM_HS15_LPHNPs and VCM_RH40_LPHNPs) were formulated and characterised for size, polydispersity index (PDI), and zeta potential (ZP). Atomistic molecular dynamics simulations revealed that both the systems self-assembled to form energetically stable aggregates. The ZP of RH40_VCM_LPHNPs changed from 0.55 ± 0.14–9.44 ± 0.33 Vm, whereas for SH15_VCM_LPHNPs, ZP changed from − 1.55 ± 0.184 Vm to 9.83 ± 0.52 Vm at pH 7.4 and 6.0, respectively. The encapsulation efficiencies of VCM were above 40% while the drug release was faster at acidic pH when compared to pH 7.4. The antibacterial activity of LPHNPs against MRSA was eight-fold better in MICs at pH 6.0, compared to 7.4, when compared to bare VCM-treated specimens. The study confirms that pH-responsive LPHNPs have the potential for enhancing the treatment of bacterial infections and other diseases characterised by acidic conditions at the target site.

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用于抗生素靶向递送的ph响应二甲基甘氨酸表面修饰支链脂质的合成

猖獗的抗菌素耐药性危机要求在感染部位有效和有针对性地给药抗生素。因此，本研究旨在合成一种ph响应的二甲基甘氨酸表面修饰支链脂质(dmgsad -脂质)。合成的脂质结构得到了充分的证实。采用溶剂蒸发法制备了脂质聚合物杂化纳米粒子(LPHNPs)，并对其进行了表征。制备了两种LPHNPs (VCM_HS15_LPHNPs和VCM_RH40_LPHNPs)，并对其大小、多分散性指数(PDI)和ZP进行了表征。原子分子动力学模拟表明，这两种系统自组装形成能量稳定的聚集体。pH值为7.4和6.0时，RH40_VCM_LPHNPs的ZP变化范围为0.55±0.14 ~ 9.44±0.33 Vm, SH15_VCM_LPHNPs的ZP变化范围为- 1.55±0.184 Vm ~ 9.83±0.52 Vm。VCM包封率在40%以上，且在酸性pH下比在pH 7.4下释放更快。LPHNPs对MRSA的抗菌活性在pH为6.0的mic中比在pH为7.4的mic中好8倍，与裸vcm处理的标本相比。该研究证实，ph反应性LPHNPs具有增强治疗细菌感染和其他以靶部位酸性条件为特征的疾病的潜力。

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来源期刊

Chemistry and Physics of Lipids 生物-生化与分子生物学

CiteScore

7.60

自引率

2.90%

发文量

审稿时长

40 days

期刊介绍： Chemistry and Physics of Lipids publishes research papers and review articles on chemical and physical aspects of lipids with primary emphasis on the relationship of these properties to biological functions and to biomedical applications. Accordingly, the journal covers: advances in synthetic and analytical lipid methodology; mass-spectrometry of lipids; chemical and physical characterisation of isolated structures; thermodynamics, phase behaviour, topology and dynamics of lipid assemblies; physicochemical studies into lipid-lipid and lipid-protein interactions in lipoproteins and in natural and model membranes; movement of lipids within, across and between membranes; intracellular lipid transfer; structure-function relationships and the nature of lipid-derived second messengers; chemical, physical and functional alterations of lipids induced by free radicals; enzymatic and non-enzymatic mechanisms of lipid peroxidation in cells, tissues, biofluids; oxidative lipidomics; and the role of lipids in the regulation of membrane-dependent biological processes.