title: Liposome-based mucus-penetrating particles (MPP) for mucosal theranostics: demonstration of diamagnetic chemical exchange saturation transfer (diaCEST) magnetic resonance imaging (MRI).
abstract: Mucus barriers lining mucosal epithelia reduce the effectiveness of nanocarrier-based mucosal drug delivery and imaging ("theranostics"). Here, we describe liposome-based mucus-penetrating particles (MPP) capable of loading hydrophilic agents, e.g., the diaCEST MRI contrast agent barbituric acid (BA). We observed that polyethylene glycol (PEG)-coated liposomes containing ≥7 mol% PEG diffused only ~10-fold slower in human cervicovaginal mucus (CVM) compared to their theoretical speeds in water. 7 mol%-PEG liposomes contained sufficient BA loading for diaCEST contrast, and provided improved vaginal distribution compared to 0 and 3mol%-PEG liposomes. However, increasing PEG content to ~12 mol% compromised BA loading and vaginal distribution, suggesting that PEG content must be optimized to maintain drug loading and stability. Non-invasive diaCEST MRI illustrated uniform vaginal coverage and longer retention of BA-loaded 7 mol%-PEG liposomes compared to unencapsulated BA. Liposomal MPP with optimized PEG content hold promise for drug delivery and imaging at mucosal surfaces.
  
  
  BACKGROUND
  This team of authors characterized liposome-based mucus-penetrating particles (MPP) capable of loading hydrophilic agents, such as barbituric acid (a diaCEST MRI contrast agent) and concluded that liposomal MPP with optimized PEG coating enables drug delivery and imaging at mucosal surfaces.
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Yu
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Sciences, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, USA; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, USA; Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Kannie W Y
authors.initials: KW
authors.lastname: Chan
authors.affiliation: Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA; Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Abraham
authors.initials: A
authors.lastname: Anonuevo
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Sciences, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, USA; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, USA.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Song
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Benjamin S
authors.initials: BS
authors.lastname: Schuster
authors.affiliation: Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA; Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Sumon
authors.initials: S
authors.lastname: Chattopadhyay
authors.affiliation: Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Qingguo
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Sciences, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, USA; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, USA.
authors.forename: Nikita
authors.initials: N
authors.lastname: Oskolkov
authors.affiliation: Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Himatkumar
authors.initials: H
authors.lastname: Patel
authors.affiliation: Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Ensign
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Sciences, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, USA; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, USA.
authors.forename: Peter C M
authors.initials: PC
authors.lastname: van Zjil
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Sciences, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, USA; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, USA; Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: mtmcmaho@gmail.com.
authors.forename: Michael T
authors.initials: MT
authors.lastname: McMahon
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA; Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: hanes@jhu.edu.
authors.forename: Justin
authors.initials: J
authors.lastname: Hanes
mesh_terms: D001463:Barbiturates / Q000737:chemistry; D002582:Cervix Mucus / Q000000981:diagnostic imaging* / Q000187:drug effects; D003287:Contrast Media; D016503:Drug Delivery Systems; D006801:Humans; D008081:Liposomes; D008279:Magnetic Resonance Imaging; D009092:Mucous Membrane / Q000000981:diagnostic imaging* / Q000473:pathology; D053758:Nanoparticles / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011859:Radiography
chemical_list: D001463:Barbiturates; D003287:Contrast Media; D008081:Liposomes; D011092:Polyethylene Glycols; C032232:barbituric acid
keywords: Barbituric acid; CEST; Drug and gene delivery; Lipid