Sifiso S. Makhathini , Calvin A. Omolo , Lucy W. Kiruri , Pavan Walvekar , Nikita Devnarain , Chunderika Mocktar , Thirumala Govender
{"title":"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","authors":"Sifiso S. Makhathini , Calvin A. Omolo , Lucy W. Kiruri , Pavan Walvekar , Nikita Devnarain , Chunderika Mocktar , Thirumala Govender","doi":"10.1016/j.chemphyslip.2022.105241","DOIUrl":null,"url":null,"abstract":"<div><p><span><span><span><span>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 </span>dimethylglycine<span> surface-modified branched lipid<span> (DMGSAD-lipid). The structure of the synthesized lipid was fully confirmed. The lipid polymer hybrid nanoparticles (LPHNPs) were formulated using the </span></span></span>solvent evaporation method and characterised. Two LPHNPs (VCM_HS15_LPHNPs and VCM_RH40_LPHNPs) were formulated and characterised for size, </span>polydispersity index (PDI), and </span>zeta potential<span><span> (ZP). Atomistic molecular dynamics simulations<span> 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 </span></span>antibacterial activity<span> 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.</span></span></p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":null,"pages":null},"PeriodicalIF":3.4000,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"Synthesis of pH-responsive dimethylglycine surface-modified branched lipids for targeted delivery of antibiotics\",\"authors\":\"Sifiso S. Makhathini , Calvin A. Omolo , Lucy W. Kiruri , Pavan Walvekar , Nikita Devnarain , Chunderika Mocktar , Thirumala Govender\",\"doi\":\"10.1016/j.chemphyslip.2022.105241\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p><span><span><span><span>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 </span>dimethylglycine<span> surface-modified branched lipid<span> (DMGSAD-lipid). The structure of the synthesized lipid was fully confirmed. The lipid polymer hybrid nanoparticles (LPHNPs) were formulated using the </span></span></span>solvent evaporation method and characterised. Two LPHNPs (VCM_HS15_LPHNPs and VCM_RH40_LPHNPs) were formulated and characterised for size, </span>polydispersity index (PDI), and </span>zeta potential<span><span> (ZP). Atomistic molecular dynamics simulations<span> 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 </span></span>antibacterial activity<span> 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.</span></span></p></div>\",\"PeriodicalId\":275,\"journal\":{\"name\":\"Chemistry and Physics of Lipids\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2022-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Chemistry and Physics of Lipids\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S000930842200069X\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chemistry and Physics of Lipids","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S000930842200069X","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Synthesis of pH-responsive dimethylglycine surface-modified branched lipids for targeted delivery of antibiotics
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.
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.
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