Influence of polymer end-chemistry on the morphology of perfluorohexane polymeric microcapsules intended as ultrasound contrast agents.
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 phase-transition 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 (19)F NMR spectroscopy.
Univ Paris-Sud, Institut Galien Paris-Sud, LabEx LERMIT, Faculté de Pharmacie, 5 rue J.B. Clément, 92296 Châtenay-Malabry, France; CNRS UMR 8612, Institut Galien Paris-Sud, LabEx LERMIT, 5 rue J.B. Clément, 92296 Châtenay-Malabry, France.
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Univ Paris-Sud, Institut Galien Paris-Sud, LabEx LERMIT, Faculté de Pharmacie, 5 rue J.B. Clément, 92296 Châtenay-Malabry, France; CNRS UMR 8612, Institut Galien Paris-Sud, LabEx LERMIT, 5 rue J.B. Clément, 92296 Châtenay-Malabry, France.
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Huang
BioCIS, Univ Paris-Sud, UMR CNRS 8076, 5 rue J.B. Clément, 92296 Châtenay-Malabry, France.
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Morvan
Univ Paris-Sud, Institut Galien Paris-Sud, LabEx LERMIT, Faculté de Pharmacie, 5 rue J.B. Clément, 92296 Châtenay-Malabry, France; CNRS UMR 8612, Institut Galien Paris-Sud, LabEx LERMIT, 5 rue J.B. Clément, 92296 Châtenay-Malabry, France.
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Fattal
Univ Paris-Sud, Institut Galien Paris-Sud, LabEx LERMIT, Faculté de Pharmacie, 5 rue J.B. Clément, 92296 Châtenay-Malabry, France; CNRS UMR 8612, Institut Galien Paris-Sud, LabEx LERMIT, 5 rue J.B. Clément, 92296 Châtenay-Malabry, France. Electronic address: nicolas.tsapis@u-psud.fr.
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Tsapis
D001672:Biocompatible Materials / Q000737:chemistry; D002214:Capsules; D003287:Contrast Media / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D004355:Drug Stability; D005466:Fluorocarbons / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D019344:Lactic Acid / Q000737:chemistry*; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D044367:Phase Transition; D011091:Polyesters / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013499:Surface Properties; D014463:Ultrasonography / Q000379:methods*; D014835:Volatilization
D001672:Biocompatible Materials; D002214:Capsules; D003287:Contrast Media; D004337:Drug Carriers; D005466:Fluorocarbons; D011091:Polyesters; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide); C078626:perflexane
Interfacial behavior; Microcapsules; Perfluorohexane; Polymer