Enhancing Gentamicin Antibacterial Activity by Co-Encapsulation with Thymoquinone in Liposomal Formulation
Raghad R. Alzahrani,
Manal M. Alkhulaifi,
Majed Al Jeraisy,
Abdulkareem M. Albekairy,
Rizwan Ali,
Bahauddeen M. Alrfaei,
Salleh N. Ehaideb,
Ahmed I. Al-Asmari,
Sultan Al Qahtani,
Abdulaziz Halwani,
Alaa Eldeen B. Yassin,
Majed A. Halwani
Affiliations
Raghad R. Alzahrani
Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
Manal M. Alkhulaifi
Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
Majed Al Jeraisy
King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia
Abdulkareem M. Albekairy
Department of Pharmacy Practice, College of Pharmacy, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia
Rizwan Ali
Medical Research Core Facility and Platforms, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia
Bahauddeen M. Alrfaei
Stem Cells and Regenerative Medicine, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, National Guard Health Affairs, Riyadh 11481, Saudi Arabia
Salleh N. Ehaideb
Experimental Medicine Department, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard—Health Affairs, Riyadh 11481, Saudi Arabia
Ahmed I. Al-Asmari
Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia
Sultan Al Qahtani
Department of Basic Medical Sciences, College of Medicine, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia
Abdulaziz Halwani
King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia
Alaa Eldeen B. Yassin
College of Pharmacy, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia
Majed A. Halwani
Nanomedicine Department, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia
Background and Purpose. Gentamicin (GEN) is a broad-spectrum antibiotic that cannot be prescribed freely because of its toxicity. Thymoquinone (THQ), a phytochemical, has antibacterial, antioxidant, and toxicity-reducing properties. However, its hydrophobicity and light sensitivity make it challenging to utilize. This incited the idea of co-encapsulating GEN and THQ in liposomes (Lipo-GEN-THQ). Method. Lipo-GEN-THQ were characterized using the zeta-potential, dynamic light scattering, Fourier transform infrared spectroscopy, and transmission electron microscope (TEM). The liposomes’ stability was evaluated under different storage and biological conditions. Lipo-GEN-THQ’s efficacy was investigated by the minimum inhibitory/bactericidal concentrations (MICs-MBCs), time–kill curves, and antibiofilm and antiadhesion assays. Bacterial interactions with the empty and GEN-THQ-loaded liposomes were evaluated using TEM. Results. The Lipo-GEN-THQ were spherical, monodispersed, and negatively charged. The Lipo-GEN-THQ were relatively stable and released GEN sustainably over 24 h. The liposomes exhibited significantly higher antibacterial activity than free GEN, as evidenced by the four-fold lower MIC and biofilm eradication in resistant E. coli strain (EC-219). TEM images display how the empty liposomes fused closely to the tested bacteria and how the loaded liposomes caused ultrastructure damage and intracellular component release. An antiadhesion assay showed that the Lipo-GEN-THQ and free GEN (0.125 mg/L) similarly inhibited Escherichia coli (EC-157) adhesion to the A549 cells (68% vs. 64%). Conclusions. The Lipo-THQ-GEN enhanced GEN by combining it with THQ within the liposomes, reducing the effective dose. The reduction in the GEN dose after adding THQ may indirectly reduce the toxicity and aid in developing an enhanced and safer form of GEN.
