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A novel antibiotic-delivery system by using ovotransferrin as targeting molecule
Hisham R Ibrahim1, Sayuri Tatsumoto1, Hajime Ono1
1Department of Biochemistry and Biotechnology, Faculty of Agriculture, Kagoshima University, Kagoshima 890-0065, Japan.
Summary
Ovotransferrin (OTf) complexes with synthetic antibiotics like sulfonamide and triclosan (TCS) improve solubility and reduce toxicity. These novel antibiotic-OTf complexes show enhanced bactericidal activity and target intracellular pathogens effectively.
Area of Science:
- Microbiology
- Drug Delivery
- Biochemistry
Background:
- Synthetic antibiotics like sulfonamide and triclosan (TCS) target essential bacterial pathways but suffer from poor solubility and high toxicity.
- Current limitations restrict the therapeutic efficiency of these valuable antimicrobial agents.
- Targeting intracellular pathways offers a promising strategy for combating bacterial infections.
Purpose of the Study:
- To explore ovotransferrin (OTf) as a carrier for targeted delivery of antibiotics, aiming to overcome solubility and toxicity issues.
- To investigate the potential of OTf-antibiotic complexes for enhanced antimicrobial efficacy and specific cellular targeting.
- To evaluate the role of transferrin receptor (TfR) mediated endocytosis in drug delivery.
Main Methods:
- Complexation of sulfa antibiotics and triclosan (TCS) with ovotransferrin (OTf) via non-covalent interactions.
- Assessment of aqueous solubility and bactericidal activity of OTf-antibiotic complexes against various bacterial strains.
- Evaluation of susceptibility in multi-drug resistant Salmonella and tolC-knockout mutant strains.
- Testing the efficacy of complexes against intracellular pathogens in infected human colon carcinoma cells (HCT-116).
Main Results:
- Complexation with OTf rendered insoluble antibiotics completely soluble in aqueous solutions.
- OTf complexes exhibited superior bactericidal activity compared to free antibiotic agents.
- Multi-drug resistant Salmonella strains and tolC-knockout mutants showed increased susceptibility to OTf complexes.
- Antibiotic-OTf complexes effectively eliminated intracellular pathogens in HCT-116 cells.
Conclusions:
- Ovotransferrin (OTf) serves as an effective carrier for improving antibiotic solubility and reducing toxicity.
- TfR-mediated endocytosis of OTf facilitates targeted drug delivery to pathogens and infected cells.
- Antibiotic-OTf complexes represent a potent strategy for the treatment of infectious diseases, including those caused by resistant strains.
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