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Surface-engineered liposomes for dual-drug delivery targeting strategy against methicillin-resistant Staphylococcus aureus(MRSA)

引用

Asian Journal of Pharmaceutical Sciences 2022年第1期17卷 102-119页

作者： Nur Najihah Izzati Mat Rani Xiang Yi Chen Zahraa M.Al-Zubaidi hanisah azhari Tzar Mohd Nizam Khaitir Pei Yuen Ng Fhataheya Buang Geok Chin Tan Yin Ping Wong Mazlina Mohd Said Adeel Masood Butt Azmy A.Hamid Mohd Cairul Iqbal Mohd Amin Centre for Drug Delivery Technology Faculty of PharmacyUniversiti Kebangsaan MalaysiaKuala Lumpur 50300Malaysia Faculty of Pharmacy and Health Sciences University Kuala Lumpur Royal College of Medicine Perak No.3Perak 30450Malaysia Department of Medical Microbiology&Immunology Faculty of MedicineUniversiti Kebangsaan MalaysiaKuala Lumpur 56000Malaysia Drug and Herbal Research Center Faculty of PharmacyUniversiti Kebangsaan MalaysiaKuala Lumpur 50300Malaysia Reading School of Pharmacy University of ReadingReading RG66ADUnited Kingdom Department of Pathology Faculty of MedicineUniversiti Kebangsaan MalaysiaKuala Lumpur 56000Malaysia Institute of Pharmaceutical Sciences University of Veterinary and Animal SciencesLahore 54000Pakistan XORIX Sdn Bhd Dungun Terengganu 23000Malaysia

This study focused on the encapsulation of vancomycin(VAN) into liposomes coated with a red blood cell membrane with a targeting ligand, daptomycin–polyethylene glycol–1,2-distearoyl-sn-glycero-3-phosphoethanolamine, formed by conjugation of DAPT and Nhydroxysuccinimidyl-polyethylene glycol-1,*** formulation is capable of providing controlled and targeted drug delivery to the bacterial cytoplasm. We performed MALDI-TOF, NMR and FTIR analyses to confirm the conjugation of the targeting ligand via the formation of amide bonds. Approximately 45% of VAN could be loaded into the aqueous cores, whereas 90% DAPT was detected using UV–vis spectrophotometry. In comparison to free drugs, the formulations controlled the release of drugs for > 72 h. Additionally, as demonstrated using CLSM and flow cytometry, the resulting formulation was capable of evading detection by macrophage cells. In comparison to free drugs, red blood cell membrane–DAPT–VAN liposomes, DAPT liposomes, and VAN liposomes reduced the MIC and significantly increased bacterial permeability, resulting in > 80% bacterial death within 4 h. Cytotoxicity tests were performed in vitro and in vivo on mammalian cells,in addition to hemolytic activity tests in human erythrocytes, wherein drugs loaded into the liposomes and RBCDVL exhibited low toxicity. Thus, the findings of this study provide insight about a dual antibiotic targeting strategy that utilizes liposomes and red blood cell membranes to deliver targeted drugs against MRSA.

关键词： Erythrocyte Dual drug delivery Liposome Methicillin-resistant staphylococcus aureus Vancomycin Daptomycin

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