Open AccessMaltoheptaose-Presenting Nanoscale Glycoliposomes for the Delivery of Rifampicin to E. coli
Author(s) -
Bin Wu,
William Ndugire,
Xuan Chen,
Mingdi Yan
Publication year - 2021
Publication title -
acs applied nano materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 29
ISSN - 2574-0970
DOI - 10.1021/acsanm.1c01320
Subject(s) - liposome , chemistry , rifampicin , phosphatidylcholine , drug delivery , concanavalin a , dissociation constant , pharmacokinetics , chromatography , biochemistry , pharmacology , phospholipid , antibiotics , receptor , in vitro , biology , organic chemistry , membrane
Liposomes, a nanoscale drug delivery system, are well known for their ability to improve pharmacokinetics and reduce drug toxicity. In this work, maltoheptaose (G7)-presenting glycoliposomes were synthesized and evaluated in the delivery of the antibiotic rifampicin. Two types of liposomes were prepared: nonfluid liposomes from l- α -phosphatidylcholine (PC) and cholesterol, and fluid liposomes from 1,2-dipalmitoyl- sn -glycero-3-phosphocholine and 1,2-dimyristoyl- sn -glycero-3-phospho-(1'-rac-glycerol). G7-derivatized glycolipid, G7-DPPE (DPPE: 1,2-dipalmitoyl- sn -glycero-3-phosphoethanolamine), was incorporated into the liposomes at 21 and 14 μ mol/mg to form nanoparticles of 75 ± 12 and 146 ± 14 nm for the nonfluid and fluid G7-glycoliposomes, respectively. The multivalent G7-glycoliposomes were characterized by lectin binding with concanavalin A (Con A). The dissociation constant K d between Con A and the nonfluid or fluid G7-glycoliposomes was 0.93 or 0.51 μ M, which represented ~900- or 1600-fold stronger affinity than the binding between Con A and G7. The G7-glycoliposomes were loaded with rifampicin at 6.6 and 16 wt % encapsulation for the nonfluid and fluid G7-glycoliposomes, respectively. Introducing a carbohydrate in the liposomes slowed down the release of rifampicin, with the G7-glycoliposomes having the slowest release rate and the lowest permeability coefficient among the liposome formulations. The fluid G7-glycoliposomes lowered the minimal inhibitory concentration (MIC) of rifampicin against E. coli ORN208 by about 3 times, whereas liposomes without G7 or Man (d-mannose)-glycoliposomes showed no improvement in MIC. The rifampicin-loaded fluid G7-glycoliposomes demonstrated the best sustained antibacterial activity against E. coli , with up to 2 log reduction in the colony forming units at 4 × MIC after 24 h. Fluorescence resonance energy transfer and confocal fluorescence microscopy revealed stronger interactions of the bacterium with the fluid G7-glycoliposomes than other liposome formulations.