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Solid Lipid Nanoparticles SLNs for Intracellular Targeting Applications
Published on: November 17, 2015
Doxycycline-encapsulated solid lipid nanoparticles as promising tool against Brucella melitensis enclosed in
Seyed Mostafa Hosseini1, Roghayyeh Abbasalipourkabir2, Farid Azizi Jalilian3
11Department of Microbiology, Faculty of Medicine, Hamadan University of Medical Sciences, Shahid fahmideh street, Park Mardome, Hamadan, IR Iran.
Background:
Brucellosis is a zoonotic disease caused by Brucella species. It has been estimated that more than 500,000 new cases of Brucellosis occur annually all around the world. Relapse of the disease is one of the most important challenges. The most important reason for the relapse of brucellosis is the survival of the bacteria inside the macrophages, which makes them safe from the immune system and disrupts drug delivery mechanism.
Objectives:
The present study was performed to assess the effects of Doxycycline-loaded Solid Lipid Nanoparticles (DOX-SLN) on the Brucella melitensis inside macrophages.
Methods:
DOX-SLN was prepared using double emulsion method. The technological characterization of DOX-SLN, including particle size, zeta potential, polydispersity index (PDI), drug loading and encapsulation efficiency were used. Fourier-transform infrared spectroscopy (FTIR) and Differential scanning calorimetry (DSC) were used to assess the interactions between Nanoparticles (NPs) components and crystalline form of doxycycline. Moreover, the effect of DOX-SLN on the bacteria were compared with that of the doxycycline using various methods, including well diffusion, Minimum Inhibitory Concentration (MIC), and investigation of their effects on murine macrophage-like cells cell line J774A.1.
Results:
The means of particle size, zeta potential, PDI, drug loading and encapsulation efficiency were 299 ± 34 nm, - 28.7 ± 3.2 mV, 0.29 ± 0.027, 11.2 ± 1.3%, and 94.9 ± 3.2%, respectively. The morphology of NPs were spherical with a smooth surface. No chemical reaction was occurred between the components. Doxycycline was located within NP matrix in its molecular form. The DOX-SLN significantly decreased the microbial loading within macrophages (3.5 Log) in comparison with the free doxycycline.
Conclusions:
Since the DOX-SLN showed better effects on B. melitensis enclosed in macrophages than the free doxycycline, it is recommended to use it for treating brucellosis and preventing relapse.
Insights
Doxycycline-loaded solid lipid nanoparticles (DOX-SLN) effectively target Brucella melitensis within macrophages, offering a promising strategy for brucellosis treatment and relapse prevention.
Area of Science:
- Nanotechnology
- Infectious Diseases
- Pharmacology
Background:
- Brucellosis is a widespread zoonotic disease with over 500,000 annual cases globally.
- Disease relapse is a significant challenge, often due to bacteria surviving within macrophages, evading immune responses and drug delivery.
- Targeting intracellular pathogens like Brucella within macrophages is crucial for effective treatment.
Purpose of the Study:
- To evaluate the efficacy of Doxycycline-loaded Solid Lipid Nanoparticles (DOX-SLN) against Brucella melitensis residing inside macrophages.
- To assess the potential of DOX-SLN in overcoming drug resistance mechanisms associated with intracellular Brucella infections.
Main Methods:
- DOX-SLN were prepared using the double emulsion method and characterized for particle size, zeta potential, PDI, drug loading, and encapsulation efficiency.
- Fourier-transform infrared spectroscopy (FTIR) and Differential scanning calorimetry (DSC) were employed to analyze NP-drug interactions and doxycycline's crystalline state.
- Antimicrobial activity was assessed via well diffusion, MIC, and evaluation of DOX-SLN's impact on Brucella-infected J774A.1 macrophage cell line.
Main Results:
- DOX-SLN exhibited optimal characteristics: particle size of 299 nm, zeta potential of -28.7 mV, PDI of 0.29, drug loading of 11.2%, and encapsulation efficiency of 94.9%.
- Characterization confirmed spherical morphology, no chemical interactions between components, and doxycycline's molecular incorporation within the NP matrix.
- DOX-SLN demonstrated a significant reduction in intracellular Brucella loading (3.5 Log) compared to free doxycycline.
Conclusions:
- DOX-SLN exhibited superior efficacy against intracellular Brucella melitensis compared to conventional doxycycline.
- The findings strongly support the use of DOX-SLN for brucellosis treatment, particularly for preventing disease relapse.
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