Influence of polymer end-chemistry on the morphology of perfluorohexane polymeric microcapsules intended as ultrasound contrast agents

摘要

Ultrasound contrast agents (UCAs) composed of a liquid perfluorocarbon (PFC) core surrounded by a polymer shell have shown promising echogenicity as well as stability. In a strategy to optimize the ultrasound properties of these systems, encapsulating a liquid PFC with a low boiling point such as perfluorohexane (PFH) was suggested. The ultimate aim of these systems would be to induce phasetransition of the liquid PFH into gas by acoustic droplet vaporization (ADV) to further increase the UCA acoustic response. Microcapsules with a perfluorohexane core have been developed by an emulsion-evaporation process, using three biodegradable polymers: PLGA and PLA with acid (PLA-COOH) and ester (PLA-COOR) terminations. Despite their similar properties, these polymers were found to strongly influence the final microcapsule morphology. While PLGA was able to form nice core-shell microcapsules, the use of PLA-COOH led to decentered microcapsules and big "eye" morphologies, and PLA-COOR induced the formation of "acorn" morphologies. To shed light on morphologies disparities, polymer interfacial behavior was studied at the dichloromethane-water and the PFH-dichloromethane interfaces. One can conclude that the core-shell structure is the result of a significant adsorption of the polymer at the dichloromethane-water interface together with a good stability of the PFH droplet within the emulsion globule. Previous work has shown that the capsule's thickness-to-radius (T/R) ratio can be controlled easily by varying the polymer to perfluorocarbon proportions. This versatility was confirmed for PFH capsules with PLA-COOH and PLGA shells. Finally, the encapsulation efficiency of PFH was assessed by relating the T/R ratio to the volume fraction of PFH and by 19F NMR spectroscopy. (C) 2014 Elsevier B. V. All rights reserved.