Physicochemical Characterization of the Shell Composition of PBCA‐Based Polymeric Microbubbles

• Published in: Macromolecular bioscience 2017-10, Vol.17 (10), p.n/a
• Main Authors: Appold, Lia, Shi, Yang, Rütten, Stephan, Kühne, Alexander, Pich, Andrij, Kiessling, Fabian, Lammers, Twan
• Format: Article
• Language: English
• Subjects: Animals; Carbocyanines - chemistry; Chains (polymeric); Chromatography, Gel; Composition; Contrast agents; Drug delivery; Drug Delivery Systems; Enbucrilate - chemical synthesis; Enbucrilate - chemistry; Excretion; Humans; Hydrogen-Ion Concentration; Kidneys; Liquid chromatography; Microbubbles; Molecular Weight; Octoxynol - chemistry; pH effects; poly(butyl cyanoacrylate); Polydispersity; Polymers; Polysorbates - chemistry; Renal function; Shells; Stirring; Surface-Active Agents - chemistry; Ultrasound
• ISSN: 1616-5187; 1616-5195
• DOI: 10.1002/mabi.201700002

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 (M n) 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. Polymeric microbubbles (MB) are useful for drug delivery purposes. The authors analyzed the influence of synthesis parameters on the molecular weight distribution of the polymer chains constituting the shell of poly(butyl cyanoacrylate) (PBCA) MB using gel permeation chromatography. More than 99% of the polymer chains composing the PBCA MB‐shell were found to be below the kidney clearance threshold of 40 kDa.