Academic Journal
Antibiotic-in-cyclodextrin-in-liposomes:formulation development and interactions with model bacterial membranes
| العنوان: | Antibiotic-in-cyclodextrin-in-liposomes:formulation development and interactions with model bacterial membranes |
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| المؤلفون: | Vandera, Kalliopi-Kelli A., Picconi, Pietro, Valero, Margarita, González-Gaitano, Gustavo, Woods, Arcadia, Zain, Nur Masirah, Bruce, Kenneth, Clifton, Luke A., Skoda, Maximilian W.A., Rahman, Khondaker Miraz, Harvey, Richard D., Dreiss, Cecile |
| المصدر: | Vandera , K-K A , Picconi , P , Valero , M , González-Gaitano , G , Woods , A , Zain , N M , Bruce , K , Clifton , L A , Skoda , M W A , Rahman , K M , Harvey , R D & Dreiss , C 2020 , ' Antibiotic-in-cyclodextrin-in-liposomes : formulation development and interactions with model bacterial membranes ' , Molecular Pharmaceutics , vol. 17 , no. 7 , pp. 2354-2369 . https://doi.org/10.1021/acs.molpharmaceut.0c00096 |
| سنة النشر: | 2020 |
| المجموعة: | King's College, London: Research Portal |
| مصطلحات موضوعية: | Langmuir monolayers, antibiotic formulation, antimicrobial resistance, asymmetric bilayer, membrane fusion, neutron reflectivity |
| الوصف: | Gram-negative bacteria possess numerous defenses against antibiotics, due to the intrinsic permeability barrier of their outer membrane (OM), explaining the recalcitrance of some common and life-threatening infections. We report the formulation of a new drug, PPA148, which shows promising activity against all Gram-negative bacteria included in the ESKAPEE pathogens. PPA148 was solubilized by inclusion complexation with cyclodextrin followed by encapsulation in liposomes. The complex and liposomal formulation presented increased activity against E. coli compared to the pure drug when assessed with the Kirby Bauer assay. The novel formulation containing 1 μg PPA148 reached similar efficacy levels equivalent to those of 30 μg of pure rifampicin. A range of biophysical techniques was used to explore the mechanism of drug uptake. Langmuir trough (LT) and neutron reflectivity (NR) techniques were employed to monitor the interactions between the drug and the formulation with model membranes. We found evidence for liposome fusion with the model Gram-negative outer membrane and for cyclodextrins acting as inner membrane (IM) permeation enhancers without presenting intrinsic antimicrobial activity. An antibiotic-in-cyclodextrin-in-liposomes (ACL) formulation was developed, which targets both the bacterial OM and IM, and offers promise as a means to breach the Gram-negative cell envelope. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| DOI: | 10.1021/acs.molpharmaceut.0c00096 |
| الاتاحة: | https://kclpure.kcl.ac.uk/portal/en/publications/35f0affa-0c8b-4dbc-8446-74a6d7ed7cee https://doi.org/10.1021/acs.molpharmaceut.0c00096 https://kclpure.kcl.ac.uk/ws/files/129400255/Antibiotic_in_cyclodextrin_in_liposomes_VANDERA_Accepted30Apr2020_ePublished30Apr2020_GREEN_AAM.pdf http://www.scopus.com/inward/record.url?scp=85087533997&partnerID=8YFLogxK |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.4A3971AB |
| قاعدة البيانات: | BASE |
| DOI: | 10.1021/acs.molpharmaceut.0c00096 |
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