title: Physicochemical Characterization of the Shell Composition of PBCA-Based Polymeric Microbubbles.
abstract: Microbubbles (MB) are routinely used as contrast agents for ultrasound (US) imaging. In recent years, MB have also attracted interest as drug delivery systems. Soft-shelled lipidic MB tend to be more advantageous for US imaging, while hard-shelled polymeric MB appear to be more suitable for drug delivery purposes because of their thicker shell and the resulting higher drug loading capacity. The physicochemical composition of the shell of polymeric MB, however, remains largely unknown. This study sets out to evaluate the molecular weight and polydispersity of the building blocks constituting the shell of poly(butyl cyanoacrylate) (PBCA) MB. Several different PBCA MB were synthesized, varying preparation parameters such as pH, surfactant, stirring speed, and stirring time. Using gel permeation chromatography, it is found that the number average molecular weight (Mn) of the polymer chains in the shell of PBCA MB is 4 kDa, and that >99% of the polymer chains are below 40 kDa. This demonstrates that virtually all polymeric building blocks in the shell of PBCA MB have a size which allows for renal excretion, thereby supporting their use for drug delivery applications.
authors.affiliation: Institute for Experimental Molecular Imaging (ExMI), RWTH Aachen University Clinic and Helmholtz Institute for Biomedical Engineering, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors.forename: Lia
authors.initials: L
authors.lastname: Appold
authors.affiliation: Institute for Experimental Molecular Imaging (ExMI), RWTH Aachen University Clinic and Helmholtz Institute for Biomedical Engineering, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors.forename: Yang
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Electron Microscopic Facility, University Hospital RWTH, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Rütten
authors.affiliation: DWI-Leibniz Institute for Interactive Materials, RWTH Aachen University, Forckenbeckstrasse 50, 52056, Aachen, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kühne
authors.affiliation: DWI-Leibniz Institute for Interactive Materials, RWTH Aachen University, Forckenbeckstrasse 50, 52056, Aachen, Germany.
authors.forename: Andrij
authors.initials: A
authors.lastname: Pich
authors.affiliation: Institute for Experimental Molecular Imaging (ExMI), RWTH Aachen University Clinic and Helmholtz Institute for Biomedical Engineering, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Kiessling
authors.affiliation: Institute for Experimental Molecular Imaging (ExMI), RWTH Aachen University Clinic and Helmholtz Institute for Biomedical Engineering, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors.forename: Twan
authors.initials: T
authors.lastname: Lammers
mesh_terms: D000818:Animals; D002232:Carbocyanines / Q000737:chemistry; D002850:Chromatography, Gel; D016503:Drug Delivery Systems; D004659:Enbucrilate / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D045423:Microbubbles; D008970:Molecular Weight; D017830:Octoxynol / Q000737:chemistry; D011136:Polysorbates / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: D002232:Carbocyanines; D011136:Polysorbates; D013501:Surface-Active Agents; C053313:1,1',3,3,3',3'-hexamethylindotricarbocyanine; D017830:Octoxynol; D004659:Enbucrilate
keywords: drug delivery; microbubbles; poly(butyl cyanoacrylate); ultrasound