Safety and Therapeutic Efficacy of Thymoquinone-Loaded Liposomes against Drug-Sensitive and Drug-Resistant Acinetobacter baumannii

Abstract

In the present study, we investigated the activity of free thymoquinone (TQ) or liposomal thymoquinone (Lip-TQ) in comparison to standard antibiotic amoxicillin (AMX) against the drug-sensitive and drug-resistant Acinetobacter baumannii. A liposomal formulation of TQ was prepared and characterized and its toxicity was evaluated by analyzing the hematological, liver and kidney function parameters. TQ was effective against both drug-sensitive and drug-resistant A. baumannii as shown by the findings of drug susceptibility testing and time kill kinetics. Moreover, the therapeutic efficacy of TQ or Lip-TQ against A. baumannii was assessed by the survival rate and the bacterial load in the lung tissues of treated mice. The mice infected with drug-sensitive A. baumannii exhibited a 90% survival rate on day 30 post treatment with Lip-TQ at a dose of 10 mg/kg, whereas the mice treated with AMX (10 mg/kg) had a 100% survival rate. On the other hand, the mice infected with drug-resistant A. baumannii had a 70% survival rate in the group treated with Lip-TQ, whereas AMX was ineffective against drug-resistant A. baumannii and all the mice died within day 30 after the treatment. Moreover, Lip-TQ treatment effectively reduced the bacterial load in the lung tissues of the mice infected with the drug-sensitive and drug-resistant A. baumannii. Moreover, the blood of the mice treated with Lip-TQ had reduced levels of inflammation markers, leukocytes and neutrophils. The results of the present study suggest that Lip-TQ may prove to be an effective therapeutic formulation in the treatment of the drug-sensitive or drug-resistant A. baumannii infection as well.

Antimicrobial, Immunomodulatory and Anti-Inflammatory Potential of Liposomal Thymoquinone: Implications in the Treatment of Bacterial Pneumonia in Immunocompromised Mice

“…Despite possessing a wide range of therapeutic properties, the clinical use of TQ has been restricted owing to its meager solubility and bioavailability. The incorporation of TQ in various drug delivery systems has augmented the therapeutic efficacy of the drug [14,16]. The results of the present study demonstrated greater activity of TQ in lipid nanoparticle formulation because A. baumannii-infected leukopenic mice treated with Lip-TQ (10 mg/kg) had a 60% survival rate on day 40 post-infection, whereas the mice in the group treated with free TQ at the same dose died before day 40 post-infection.…”

“…The liposomal formulation of TQ was prepared and characterized as described earlier [16]. All the constituents, including PC, Chol, and TQ, were dissolved in a methanol and chloroform mixture (1:1 Vol/Vol) in a round-bottom flask.…”

“…The efficacy of the therapy was evaluated by examining the load of A. baumannii in the lung tissues [16]. On day 7, three mice were randomly selected from each group and sacrificed to excise the lungs.…”

New Broth Macrodilution Volatilization Method for Antibacterial Susceptibility Testing of Volatile Agents and Evaluation of Their Toxicity Using Modified MTT Assay In Vitro

“…However, their specific structural and technological modifications reducing toxicity are possible. For example, liposomal encapsulation of thymoquinone was found to be effective in decreasing its toxic effects [ 52 ].…”

Liposome-Mediated Delivery of MERS Antigen Induces Potent Humoral and Cell-Mediated Immune Response in Mice

“…1 − A Free antigen /A Total antigen (1) where A Free antigen is the amount of antigen present in the supernatant; A Total antigen is the amount of total antigen initially added. The size and shape of the DRVs were determined by transmission electron microscopy (TEM), whereas the polydispersity index (PDI) and zeta potential were revealed by the Malvern Nano Zeta Sizer (Malvern Instruments, Southborough, MA, USA), using the dynamic light scattering (DLS) technique as previously described [22].…”