Engineering the Acoustic Response and Drug Loading Capacity of PBCA-Based Polymeric Microbubbles with Surfactants.

Autor: Barmin RA; Institute for Experimental Molecular Imaging, RWTH Aachen University Hospital, 52074 Aachen, Germany., Dasgupta A; Institute for Experimental Molecular Imaging, RWTH Aachen University Hospital, 52074 Aachen, Germany., Bastard C; DWI - Leibniz Institute for Interactive Materials, 52074 Aachen, Germany.; Institute for Technical and Macromolecular Chemistry, RWTH Aachen University, 52074 Aachen, Germany.; Institute of Applied Medical Engineering, Department of Advanced Materials for Biomedicine, RWTH Aachen University, 52074 Aachen, Germany., De Laporte L; DWI - Leibniz Institute for Interactive Materials, 52074 Aachen, Germany.; Institute for Technical and Macromolecular Chemistry, RWTH Aachen University, 52074 Aachen, Germany.; Institute of Applied Medical Engineering, Department of Advanced Materials for Biomedicine, RWTH Aachen University, 52074 Aachen, Germany., Rütten S; Electron Microscope Facility, RWTH Aachen University Hospital, 52074 Aachen, Germany., Weiler M; Institute for Experimental Molecular Imaging, RWTH Aachen University Hospital, 52074 Aachen, Germany., Kiessling F; Institute for Experimental Molecular Imaging, RWTH Aachen University Hospital, 52074 Aachen, Germany., Lammers T; Institute for Experimental Molecular Imaging, RWTH Aachen University Hospital, 52074 Aachen, Germany., Pallares RM; Institute for Experimental Molecular Imaging, RWTH Aachen University Hospital, 52074 Aachen, Germany.
Jazyk: angličtina
Zdroj: Molecular pharmaceutics [Mol Pharm] 2022 Sep 05; Vol. 19 (9), pp. 3256-3266. Date of Electronic Publication: 2022 Jul 29.
DOI: 10.1021/acs.molpharmaceut.2c00416
Abstrakt: Gas-filled microbubbles (MB) are routinely used in the clinic as ultrasound contrast agents. MB are also increasingly explored as drug delivery vehicles based on their ultrasound stimuli-responsiveness and well-established shell functionalization routes. Broadening the range of MB properties can enhance their performance in both imaging and drug delivery applications. This can be promoted by systematically varying the reagents used in the synthesis of MB, which in the case of polymeric MB include surfactants. We therefore set out to study the effect of key surfactant characteristics, such as the chemical structure, molecular weight, and hydrophilic-lipophilic balance on the formation of poly(butyl cyanoacrylate) (PBCA) MB, as well as on their properties, including shell thickness, drug loading capacity, ultrasound contrast, and acoustic stability. Two different surfactant families ( i.e. , Triton X and Tween) were employed, which show opposite molecular weight vs hydrophilic-lipophilic balance trends. For both surfactant types, we found that the shell thickness of PBCA MB increased with higher-molecular-weight surfactants and that the resulting MB with thicker shells showed higher drug loading capacities and acoustic stability. Furthermore, the higher proportion of smaller polymer chains of the Triton X-based MB (as compared to those of the Tween-based ones) resulted in lower polymer entanglement, improving drug loading capacity and ultrasound contrast response. These findings open up new avenues to fine-tune the shell properties of polymer-based MB for enhanced ultrasound imaging and drug delivery applications.
Databáze: MEDLINE