Biodegradable polymeric microcapsules for selective ultrasound-triggered drug release

Lensen, Dennis; Gelderblom, Erik; Vriezema, Dennis M.; Marmottant, Philippe; Verdonschot, Nico; Versluis, Michel; Jong, Nico de; Hest, Jan C. M. van

doi:10.1039/c1sm05324h

Cited by 70 publications

(66 citation statements)

References 31 publications

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“…Considerable effort has been devoted to achieving this goal via incorporation of functional materials or nanoparticles into the microcapsule shell to control the release of the contents of the microcapsules through the application of an external stimulus, 1-3 such as pH, 4-7 temperature, [8][9][10] light, [11][12][13] ultrasound, [14][15][16][17] glucose 18,19 and magnetic field, [20][21][22] at the appropriate time. Significant progress has been achieved to develop such controlled release methods; however, methods with better controllability are still in demand.…”

Section: Introductionmentioning

confidence: 99%

Bio-inspired controlled release through compression–relaxation cycles of microcapsules

et al. 2015

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The aim of microencapsulation is to achieve controllable and sustainable release at the desired site. Despite the many methods developed in recent years, there is still a need to advance the strategies for higher controllability and scalability. Taking inspiration from the heart, which pumps blood by continual contraction of muscles, we demonstrate a novel releasing method, in which the core release is controlled by the compression-relaxation cycles of microcapsules upon the application of a magnetic field. This idea is realized by embedding Fe 3 O 4 particles into a polymer shell. When the magnetic field is applied, the Fe 3 O 4 particles align along the field direction and stretch the shell, resulting in compression of the microcapsules and release of the core contents; the shape is restored after the field is removed. We demonstrated various release patterns by altering the strength of the magnetic field and the compression frequency. This release method provides repeated and pulsatile delivery, enhanced spreading distance and ejection speed, and is site specific and proactive, providing a new option for controlled release applications.

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Section: Introductionmentioning

confidence: 99%

Bio-inspired controlled release through compression–relaxation cycles of microcapsules

et al. 2015

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“…If contrast enhancement is not the primary consideration, then polymercoated microbubbles can offer several advantages for drug encapsulation; in particular the relative ease with which their size, shell thickness and drug loading can be controlled [101][102][103][104] . Polymer coatings can also be readily functionalized for molecular targeting 105 .…”

Section: Functionalized and Drug-loaded Microbubblesmentioning

confidence: 99%

Ultrasound contrast agents: bubbles drops and particles

Lajoinie¹

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The research described in this thesis is part of the research program NanoNextNL, a micro and nanotechnology consortium of the Government of the Netherlands and 130 partners. This thesis was carried out at the Physics of Fluids group of the Faculty of Science and Technology of the University of Twente. Cover design:As a representation of a crucial goal of this work, the cover depicts a confocal microscopy image showing cells selectively porated by loaded microbubbles upon ultrasound exposure. The porated cells take up a blue fluorescent probe. By Ine Lentacker, Ine De Cock and Guillaume Lajoinie. Guide through the thesisIn this thesis, we investigate different types of innovative agents, designed for biomedical use in a context of molecular imaging. In Chapter 1, we review the agents that arouse the interest of the scientific community, most of them at the research stage of development, together with the experimental methods that can be used to study their interaction with cells. Such in vitro investigations are necessary to test on short scales the impact of the various agents on biological structures.We separate the agents in three main categories. The first group consists of stabilized microbubbles, usually by means of phospholipids that fill up the interfacial area between the gas core and the surrounding liquid (water). Such bubbles are clinically used for 40 years as contrast agents for ultrasound owing to their unique resonance behavior. When irradiated with an ultrasound pulse, a bubble experiences volumetric oscillations, that reemit an ultrasound wave back to the transducer. This process makes them unchallenged ultrasound scatterers. The role of these stable microbubbles in new biomedical research directions is discussed in Chapters 2 to 9.Phospholipid coatings were developed in the last decade to do much more than just prevent bubble dissolution. They are now a crucial tool to enrich the microbubbles with specific markers or drug payloads. In Chapter 2, we investigate the behavior of this coating when the microbubbles are subjected to an ultrasound field. We show that the coating is shed away from the microbubble, which is of major interest for molecular imaging combined with drug delivery using microbubbles. We pursue the idea in Chapter 3 where we investigate how a bubble payload, here liposomes labeled with a fluorescent dye, is released under ultrasound exposure. In Chapter 4, we link these direct observations of shedding of the previous Chapters to the subsequent dissolution of the microbubbles, no longer protected by a phospholipid shell. This dissolution, visible in the ultrasound scatter spectrum can be used to remotely quantify the effect of the microbubbles. In support of these observations, we dedicate the next Chapter (Chapter 5) to physically understand the mechanisms underlying the behavior of the phospholipid coating. The application of these findings in practice requires the production a sufficiently high production rate and with great control of such microbubbles. In Chapter 6, we th...

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“…Hard-shelled water-filled microspheres are formed when the solvent is evaporated. The capsules are then washed to remove excess solvent, then freeze-dried to produce gas-filled capsules 58 . A narrow size distribution can be obtained by membrane emulsification of a premix of polymer, polymer solvent and water through a mono-sized porous membrane, see Fig.…”

Section: Microbubble Formationmentioning

confidence: 99%

Monodisperse bubbles and droplets for medical applications

Segers¹

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Biodegradable polymeric microcapsules for selective ultrasound-triggered drug release

Cited by 70 publications

References 31 publications

Bio-inspired controlled release through compression–relaxation cycles of microcapsules

Bio-inspired controlled release through compression–relaxation cycles of microcapsules

Ultrasound contrast agents: bubbles drops and particles

Monodisperse bubbles and droplets for medical applications

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