Eman Elhassan, Calvin A Omolo, Mohammed Ali Gafar, Lucy W Kiruri, Usri H Ibrahim, Eman A Ismail, Nikita Devnarain, Thirumala Govender
{"title":"受疾病启发设计仿生单宁酸基混合纳米载体,用于加强细菌引发的败血症的治疗。","authors":"Eman Elhassan, Calvin A Omolo, Mohammed Ali Gafar, Lucy W Kiruri, Usri H Ibrahim, Eman A Ismail, Nikita Devnarain, Thirumala Govender","doi":"10.1021/acs.molpharmaceut.4c00048","DOIUrl":null,"url":null,"abstract":"<p><p>This study explored the development of novel biomimetic tannic acid-based hybrid nanocarriers (HNs) for targeted delivery of ciprofloxacin (CIP-loaded TAH-NPs) against bacterial-induced sepsis. The prepared CIP-loaded TAH-NPs exhibited appropriate physicochemical characteristics and demonstrated biocompatibility and nonhemolytic properties. Computational simulations and microscale thermophoresis studies validated the strong binding affinity of tannic acid (TA) and its nanoformulation to human Toll-like receptor 4, surpassing that of the natural substrate lipopolysaccharide (LPS), suggesting a potential competitive inhibition against LPS-induced inflammatory responses. CIP released from TAH-NPs displayed a sustained release profile over 72 h. The <i>in vitro</i> antibacterial activity studies revealed that CIP-loaded TAH-NPs exhibited enhanced antibacterial efficacy and efflux pump inhibitory activity. Specifically, they showed a 3-fold increase in biofilm eradication activity against MRSA and a 2-fold increase against <i>P. aeruginosa</i> compared to bare CIP. Time-killing assays demonstrated complete bacterial clearance within 8 h of treatment with CIP-loaded TAH-NPs. <i>In vitro</i> DPPH scavenging and anti-inflammatory investigations confirmed the ability of the prepared hybrid nanosystem to neutralize reactive oxygen species (ROS) and modulate LPS-induced inflammatory responses. Collectively, these results suggest that CIP-loaded TAH-NPs may serve as an innovative nanocarrier for the effective and targeted delivery of antibiotics against bacterial-induced sepsis.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"4924-4946"},"PeriodicalIF":4.5000,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Disease-Inspired Design of Biomimetic Tannic Acid-Based Hybrid Nanocarriers for Enhancing the Treatment of Bacterial-Induced Sepsis.\",\"authors\":\"Eman Elhassan, Calvin A Omolo, Mohammed Ali Gafar, Lucy W Kiruri, Usri H Ibrahim, Eman A Ismail, Nikita Devnarain, Thirumala Govender\",\"doi\":\"10.1021/acs.molpharmaceut.4c00048\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>This study explored the development of novel biomimetic tannic acid-based hybrid nanocarriers (HNs) for targeted delivery of ciprofloxacin (CIP-loaded TAH-NPs) against bacterial-induced sepsis. The prepared CIP-loaded TAH-NPs exhibited appropriate physicochemical characteristics and demonstrated biocompatibility and nonhemolytic properties. Computational simulations and microscale thermophoresis studies validated the strong binding affinity of tannic acid (TA) and its nanoformulation to human Toll-like receptor 4, surpassing that of the natural substrate lipopolysaccharide (LPS), suggesting a potential competitive inhibition against LPS-induced inflammatory responses. CIP released from TAH-NPs displayed a sustained release profile over 72 h. The <i>in vitro</i> antibacterial activity studies revealed that CIP-loaded TAH-NPs exhibited enhanced antibacterial efficacy and efflux pump inhibitory activity. Specifically, they showed a 3-fold increase in biofilm eradication activity against MRSA and a 2-fold increase against <i>P. aeruginosa</i> compared to bare CIP. Time-killing assays demonstrated complete bacterial clearance within 8 h of treatment with CIP-loaded TAH-NPs. <i>In vitro</i> DPPH scavenging and anti-inflammatory investigations confirmed the ability of the prepared hybrid nanosystem to neutralize reactive oxygen species (ROS) and modulate LPS-induced inflammatory responses. 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Disease-Inspired Design of Biomimetic Tannic Acid-Based Hybrid Nanocarriers for Enhancing the Treatment of Bacterial-Induced Sepsis.
This study explored the development of novel biomimetic tannic acid-based hybrid nanocarriers (HNs) for targeted delivery of ciprofloxacin (CIP-loaded TAH-NPs) against bacterial-induced sepsis. The prepared CIP-loaded TAH-NPs exhibited appropriate physicochemical characteristics and demonstrated biocompatibility and nonhemolytic properties. Computational simulations and microscale thermophoresis studies validated the strong binding affinity of tannic acid (TA) and its nanoformulation to human Toll-like receptor 4, surpassing that of the natural substrate lipopolysaccharide (LPS), suggesting a potential competitive inhibition against LPS-induced inflammatory responses. CIP released from TAH-NPs displayed a sustained release profile over 72 h. The in vitro antibacterial activity studies revealed that CIP-loaded TAH-NPs exhibited enhanced antibacterial efficacy and efflux pump inhibitory activity. Specifically, they showed a 3-fold increase in biofilm eradication activity against MRSA and a 2-fold increase against P. aeruginosa compared to bare CIP. Time-killing assays demonstrated complete bacterial clearance within 8 h of treatment with CIP-loaded TAH-NPs. In vitro DPPH scavenging and anti-inflammatory investigations confirmed the ability of the prepared hybrid nanosystem to neutralize reactive oxygen species (ROS) and modulate LPS-induced inflammatory responses. Collectively, these results suggest that CIP-loaded TAH-NPs may serve as an innovative nanocarrier for the effective and targeted delivery of antibiotics against bacterial-induced sepsis.
期刊介绍:
Molecular Pharmaceutics publishes the results of original research that contributes significantly to the molecular mechanistic understanding of drug delivery and drug delivery systems. The journal encourages contributions describing research at the interface of drug discovery and drug development.
Scientific areas within the scope of the journal include physical and pharmaceutical chemistry, biochemistry and biophysics, molecular and cellular biology, and polymer and materials science as they relate to drug and drug delivery system efficacy. Mechanistic Drug Delivery and Drug Targeting research on modulating activity and efficacy of a drug or drug product is within the scope of Molecular Pharmaceutics. Theoretical and experimental peer-reviewed research articles, communications, reviews, and perspectives are welcomed.