title: Pegylated oleic acid: A promising amphiphilic polymer for nano-antibiotic delivery.
abstract: Vancomycin (VM), a last resort to control methicillin-resistant S. aureus (MRSA) infections, is on the verge of becoming ineffective. Novel nano delivery systems of VM have the potential to combat MRSA. The search for novel materials for nanoantibiotic development is therefore an active research area. In this study, oleic acid (OA) was coupled with monomethoxy polyethylene glycol (mPEG) to obtain a novel bio-safe amphiphilic polymer, mPEG-OA. The critical micelle concentration of mPEG-OA, was found to be 4.5×10-8m/L. VM-loaded polymersomes were prepared from mPEG-OA and evaluated for size, polydispersity index (PDI), zeta potential (ZP), surface morphology, drug release, in vitro and in vivo antibacterial activity. The size, PDI and ZP of VM-loaded polymersomes were 142.9±7.5nm, 0.228±0.03 and -18.3±3.55mV respectively. Transmission electron microscopy images revealed the spherical shape of polymersomes. The encapsulation efficiency was 53.64±1.86%. The drug release from polymersomes was sustained and in vitro antibacterial activity was 42- and 5-fold more against S. aureus and MRSA, compared with plain VM. An in vivo BALB/c mice, skin infection models revealed that treatment with VM-loaded polymersomes significantly reduced the MRSA burden compared with plain VM and blank polymersomes. There was a 183 and a 25-fold reduction in the MRSA colony finding units load in mice skin treated with VM-loaded polymersomes compared to that treated with blank polymersomes and bare VM respectively. In summary, the developed VM-loaded polymersomes from novel mPEG-OA polymer were found to be a promising nanoantibiotic against MRSA.
authors.affiliation: Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa.
authors.forename: Calvin A
authors.initials: CA
authors.lastname: Omolo
authors.affiliation: Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa. Electronic address: rahul.kalhapure@rediffmail.com.
authors.forename: Rahul S
authors.initials: RS
authors.lastname: Kalhapure
authors.affiliation: Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa.
authors.forename: Mahantesh
authors.initials: M
authors.lastname: Jadhav
authors.affiliation: Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Rambharose
authors.affiliation: Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa.
authors.forename: Chunderika
authors.initials: C
authors.lastname: Mocktar
authors.affiliation: School of Pharmacy & Pharmaceutical Sciences, St. John's University of Tanzania, P.O. Box 47, Dodoma, Tanzania.
authors.forename: Valence M K
authors.initials: VM
authors.lastname: Ndesendo
authors.affiliation: Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa. Electronic address: govenderth@ukzn.ac.za.
authors.forename: Thirumala
authors.initials: T
authors.lastname: Govender
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002152:Calorimetry, Differential Scanning; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D051379:Mice; D008826:Microbial Sensitivity Tests; D046529:Microscopy, Electron, Transmission; D036103:Nanotechnology; D019301:Oleic Acid / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D014640:Vancomycin / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D011108:Polymers; D019301:Oleic Acid; D011092:Polyethylene Glycols; D014640:Vancomycin
keywords: Antibiotic resistance; Methicillin-resistant S. aureus; Oleic acid; Polyethylene glycol; Polymersomes; Vancomycin