Pegylated oleic acid: A promising amphiphilic polymer for nano-antibiotic delivery

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• 作者：Calvin A. Omolo^a ; Rahul S. Kalhapure^a ; ^{rahul.kalhapure@rediffmail.com} ; ^{kalhapure@ukzn.ac.za} ; Mahantesh Jadhav^a ; Sanjeev Rambharose^a ; Chunderika Mocktar^a ; Valence M.K. Ndesendo^b ; Thirumala Govender^a ; ^{govenderth@ukzn.ac.za}
• 关键词：Oleic acid ; Polyethylene glycol ; Polymersomes ; Vancomycin ; Antibiotic resistance ; Methicillin-resistant S. aureus
• 刊名：European Journal of Pharmaceutics and Biopharmaceutics
• 出版年：2017
• 出版时间：March 2017
• 年：2017
• 卷：112
• 期：Complete
• 页码：96-108
• 全文大小：2758 K
• 卷排序：112

文摘

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 × 10−8 m/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 ± 7.5 nm, 0.228 ± 0.03 and −18.3 ± 3.55 mV 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.