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<p>Antimicrobial resistance has become one of the most pressing global health challenges, with multidrug-resistant (MDR) bacterial pathogens increasingly rendering conventional therapies ineffective. Among naturally derived antimicrobials, diallyl sulphide (DAS), a bioactive organosulfur compound from garlic, holds considerable promise due to its potent antibacterial properties; however, its clinical translation remains constrained by inherent limitations in stability and bioavailability. To address these challenges, this study explores the synthesis of DAS-loaded solid lipid nanoparticles (DAS-SLN) as a targeted nano-delivery strategy against MDR <i>Bacillus cereus.</i> The DAS-SLN were fabricated using stearic acid as the lipid matrix, stabilized with Tween 80 and soy lecithin as surfactant and cosurfactant, respectively, <i>via</i> a hot emulsification low temperature solidification method and subjected to comprehensive physicochemical and biological characterisation. The resulting DAS-SLN exhibited uniform spherical morphology with particle sizes ranging from 90 to 120&#xa0;nm and a high negative zeta potential (− 37.17 ± 0.25 mV), collectively reflecting excellent colloidal stability. Encapsulation efficiency and drug loading reached 87.24 ± 4.72% and 18.12 ± 2.51%, respectively, and FTIR analysis confirmed successful DAS encapsulation without any structural modification to the compound. In vitro release studies demonstrated a biphasic release profile, characterized by an initial burst release followed by sustained drug release for up to 76&#xa0;hours. Kinetic modeling revealed a strong correlation with the Korsmeyer–Peppas model, indicating a non-Fickian (anomalous) transport mechanism governed by a combination of diffusion and matrix relaxation, thereby confirming the controlled and prolonged release behavior of the formulation. Notably, DAS-SLN showed significantly enhanced antibacterial efficacy compared to free DAS, reflected by a reduced minimum inhibitory concentration (MIC) of 0.15 ± 0.03% (w/v), complete bacterial eradication, and robust antibiofilm inhibition of 89.61 ± 5.28%. Mechanistic investigations through protein leakage assays, propidium iodide (PI) uptake, and scanning electron microscopy (SEM) collectively confirmed membrane-level disruption as the primary mode of action. Furthermore, the notable antioxidant activity exhibited by DAS-SLN suggests an additional dimension of therapeutic benefit through oxidative stress modulation. Taken together, these findings position DAS-SLN as an eco-compatible, multi-functional nanotherapeutic platform with strong translational potential for the management of MDR <i>B. cereus</i> infections.</p> Graphical Abstract <p></p>

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Encapsulation of Diallyl Sulphide in Solid Lipid Nanoparticles to Combat Multi-Drug Resistance Bacillus cereus

  • 期刊论文

  • 发表日期：

    2026年4月30日

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  • Manish Kumar Manjhi,
  • Abhishek Pathak,
  • Kuldeep Gauliya,
  • Neetesh Mandal,
  • Devanshi Chandel Upadhyay,
  • Chandrama Prakash Upadhyay

摘要

Antimicrobial resistance has become one of the most pressing global health challenges, with multidrug-resistant (MDR) bacterial pathogens increasingly rendering conventional therapies ineffective. Among naturally derived antimicrobials, diallyl sulphide (DAS), a bioactive organosulfur compound from garlic, holds considerable promise due to its potent antibacterial properties; however, its clinical translation remains constrained by inherent limitations in stability and bioavailability. To address these challenges, this study explores the synthesis of DAS-loaded solid lipid nanoparticles (DAS-SLN) as a targeted nano-delivery strategy against MDR Bacillus cereus. The DAS-SLN were fabricated using stearic acid as the lipid matrix, stabilized with Tween 80 and soy lecithin as surfactant and cosurfactant, respectively, via a hot emulsification low temperature solidification method and subjected to comprehensive physicochemical and biological characterisation. The resulting DAS-SLN exhibited uniform spherical morphology with particle sizes ranging from 90 to 120 nm and a high negative zeta potential (− 37.17 ± 0.25 mV), collectively reflecting excellent colloidal stability. Encapsulation efficiency and drug loading reached 87.24 ± 4.72% and 18.12 ± 2.51%, respectively, and FTIR analysis confirmed successful DAS encapsulation without any structural modification to the compound. In vitro release studies demonstrated a biphasic release profile, characterized by an initial burst release followed by sustained drug release for up to 76 hours. Kinetic modeling revealed a strong correlation with the Korsmeyer–Peppas model, indicating a non-Fickian (anomalous) transport mechanism governed by a combination of diffusion and matrix relaxation, thereby confirming the controlled and prolonged release behavior of the formulation. Notably, DAS-SLN showed significantly enhanced antibacterial efficacy compared to free DAS, reflected by a reduced minimum inhibitory concentration (MIC) of 0.15 ± 0.03% (w/v), complete bacterial eradication, and robust antibiofilm inhibition of 89.61 ± 5.28%. Mechanistic investigations through protein leakage assays, propidium iodide (PI) uptake, and scanning electron microscopy (SEM) collectively confirmed membrane-level disruption as the primary mode of action. Furthermore, the notable antioxidant activity exhibited by DAS-SLN suggests an additional dimension of therapeutic benefit through oxidative stress modulation. Taken together, these findings position DAS-SLN as an eco-compatible, multi-functional nanotherapeutic platform with strong translational potential for the management of MDR B. cereus infections.

Graphical Abstract