Novel formulation of antimicrobial peptides enhances antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA).
Mbuso Faya, Heba A Hazzah, Calvin A Omolo, Nikhi Agrawal, Ruma Maji, Pavan Walvekar, Chunderika Mocktar, Bongani Nkambule, Sanjeev Rambharose, Fernando Albericio, Beatriz G de la Torre, Thirumala Govender
Author Information
Mbuso Faya: Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Private Bag, Durban, X54001, South Africa. ORCID
Heba A Hazzah: Peptide Science Laboratory, School of Chemistry and Physics, University of KwaZulu-Natal, Durban, 4001, South Africa.
Calvin A Omolo: Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Private Bag, Durban, X54001, South Africa.
Nikhi Agrawal: Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Private Bag, Durban, X54001, South Africa.
Ruma Maji: Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Private Bag, Durban, X54001, South Africa.
Pavan Walvekar: Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Private Bag, Durban, X54001, South Africa.
Chunderika Mocktar: Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Private Bag, Durban, X54001, South Africa.
Bongani Nkambule: School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Private Bag, Durban, X54001, South Africa.
Sanjeev Rambharose: Department of Surgery, Division of Emergency Medicine, University of Cape Town, Cape Town, South Africa.
Fernando Albericio: Peptide Science Laboratory, School of Chemistry and Physics, University of KwaZulu-Natal, Durban, 4001, South Africa.
Beatriz G de la Torre: KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal Durban, Durban, 4041, South Africa.
Thirumala Govender: Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Private Bag, Durban, X54001, South Africa. govenderth@ukzn.ac.za.
Antimicrobial peptides (AMPs) have the ability to penetrate as well as transport cargo across bacterial cell membranes, and they have been labeled as exceptional candidates to function in drug delivery. The aim of this study was to investigate the effectiveness of novel formulation of AMPs for enhanced MRSA activity. The strategy was carried out through the formulation of liposomes by thin-layer film hydration methodology, containing phosphatidylcholine, cholesterol, oleic acid, the novel AMP, as well as vancomycin (VCM). Characterization of the AMPs and liposomes included HPLC and LCMS for peptide purity and mass determination; DLS (size, polydispersity, zeta potential), TEM (surface morphology), dialysis (drug release), broth dilution, and flow cytometry (antibacterial activity); MTT assay, haemolysis and intracellular antibacterial studies. The size, PDI, and zeta potential of the drug-loaded AMP-Lipo-1 were 102.6 ± 1.81 nm, 0.157 ± 0.01, and - 9.81 ± 1.69 mV, respectively, while for AMP-Lipo-2 drug-loaded formulation, it was 146.4 ± 1.90 nm, 0.412 ± 0.05, and - 4.27 ± 1.25 mV respectively at pH 7.4. However, in acidic pH for both formulations, we observed an increase in size, PDI, and a switch to positive zeta potential, which indicated the pH responsiveness of our liposomal systems. The in vitro drug release studies demonstrated that liposomal formulations released VCM-HCl at a faster rate at pH 6.0 compared to pH 7.4. In vitro antibacterial activity against S. aureus and MRSA revealed that liposomes had enhanced activity at pH 6 compared to pH 7.4. The study revealed that the formulation can potentially be used to enhance activity and penetration of AMPs, thereby improving the treatment of bacterial infections.
