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

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 

机构地区：[1]Centre for Drug Delivery Technology,Faculty of Pharmacy,Universiti Kebangsaan Malaysia,Kuala Lumpur 50300,Malaysia [2]Faculty of Pharmacy and Health Sciences,University Kuala Lumpur Royal College of Medicine Perak No.3,Perak 30450,Malaysia [3]Department of Medical Microbiology&Immunology,Faculty of Medicine,Universiti Kebangsaan Malaysia,Kuala Lumpur 56000,Malaysia [4]Drug and Herbal Research Center,Faculty of Pharmacy,Universiti Kebangsaan Malaysia,Kuala Lumpur 50300,Malaysia [5]Reading School of Pharmacy,University of Reading,Reading RG66AD,United Kingdom [6]Department of Pathology,Faculty of Medicine,Universiti Kebangsaan Malaysia,Kuala Lumpur 56000,Malaysia [7]Institute of Pharmaceutical Sciences,University of Veterinary and Animal Sciences,Lahore 54000,Pakistan [8]XORIX Sdn Bhd,Dungun Terengganu 23000,Malaysia

出　　处：《Asian Journal of Pharmaceutical Sciences》2022年第1期102-119,共18页亚洲药物制剂科学（英文）

基　　金：Universiti Kebangsaan Malaysia’s research university grant scheme (DCP-2017- 003/4)。

摘　　要：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-1,2-distearoyl-sn-glycero-3-phosphoethanolamine.This 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 

分 类 号：R965[医药卫生—药理学]