The role of acoustofluidics and microbubble dynamics for therapeutic applications and drug delivery

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Abstract

Targeted drug delivery is proposed to reduce the toxic effects of conventional therapeutic methods. For that purpose, nanoparticles are loaded with drugs called nanocarriers and directed toward a specific site. However, biological barriers challenge the nanocarriers to convey the drug to the target site effectively. Different targeting strategies and nanoparticle designs are used to overcome these barriers. Ultrasound is a new, safe, and non-invasive drug targeting method, especially when combined with microbubbles. Microbubbles oscillate under the effect of the ultrasound, which increases the permeability of endothelium, hence, the drug uptake to the target site. Consequently, this new technique reduces the dose of the drug and avoids its side effects. This review aims to describe the biological barriers and the targeting types with the critical features of acoustically driven microbubbles focusing on biomedical applications. The theoretical part covers the historical developments in microbubble models for different conditions: microbubbles in an incompressible and compressible medium and bubbles encapsulated by a shell. The current state and the possible future directions are discussed.

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Engineering precision nanoparticles for drug delivery

Michael J. Mitchell, Margaret M. Billingsley, Rebecca M. Haley … (2020)

In recent years, the development of nanoparticles has expanded into a broad range of clinical applications. Nanoparticles have been developed to overcome the limitations of free therapeutics and navigate biological barriers — systemic, microenvironmental and cellular — that are heterogeneous across patient populations and diseases. Overcoming this patient heterogeneity has also been accomplished through precision therapeutics, in which personalized interventions have enhanced therapeutic efficacy. However, nanoparticle development continues to focus on optimizing delivery platforms with a one-size-fits-all solution. As lipid-based, polymeric and inorganic nanoparticles are engineered in increasingly specified ways, they can begin to be optimized for drug delivery in a more personalized manner, entering the era of precision medicine. In this Review, we discuss advanced nanoparticle designs utilized in both non-personalized and precision applications that could be applied to improve precision therapies. We focus on advances in nanoparticle design that overcome heterogeneous barriers to delivery, arguing that intelligent nanoparticle design can improve efficacy in general delivery applications while enabling tailored designs for precision applications, thereby ultimately improving patient outcome overall.

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Principles of nanoparticle design for overcoming biological barriers to drug delivery.

Elvin Blanco, Haifa Shen, Mauro Ferrari (2015)

Biological barriers to drug transport prevent successful accumulation of nanotherapeutics specifically at diseased sites, limiting efficacious responses in disease processes ranging from cancer to inflammation. Although substantial research efforts have aimed to incorporate multiple functionalities and moieties within the overall nanoparticle design, many of these strategies fail to adequately address these barriers. Obstacles, such as nonspecific distribution and inadequate accumulation of therapeutics, remain formidable challenges to drug developers. A reimagining of conventional nanoparticles is needed to successfully negotiate these impediments to drug delivery. Site-specific delivery of therapeutics will remain a distant reality unless nanocarrier design takes into account the majority, if not all, of the biological barriers that a particle encounters upon intravenous administration. By successively addressing each of these barriers, innovative design features can be rationally incorporated that will create a new generation of nanotherapeutics, realizing a paradigmatic shift in nanoparticle-based drug delivery.

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Stimuli-responsive nanocarriers for drug delivery.

Simona Mura, Julien Nicolas, Patrick Couvreur … (2013)

Spurred by recent progress in materials chemistry and drug delivery, stimuli-responsive devices that deliver a drug in spatial-, temporal- and dosage-controlled fashions have become possible. Implementation of such devices requires the use of biocompatible materials that are susceptible to a specific physical incitement or that, in response to a specific stimulus, undergo a protonation, a hydrolytic cleavage or a (supra)molecular conformational change. In this Review, we discuss recent advances in the design of nanoscale stimuli-responsive systems that are able to control drug biodistribution in response to specific stimuli, either exogenous (variations in temperature, magnetic field, ultrasound intensity, light or electric pulses) or endogenous (changes in pH, enzyme concentration or redox gradients).