Polymeric carriers: role of geometry in drug delivery

Simone, Eric; Dziubla, Thomas D.; Muzykantov, Vladimir R.

doi:10.1517/17425240802567846

Cited by 196 publications

(144 citation statements)

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“…The motivation to develop particles with switchable shapes comes from the fact that shape has recently emerged as a crucial design parameter of micro-and nanoparticles (3,4,33,38,39). Studies have demonstrated that departure from the conventional spherical shape of particles brings unique and improved functionalities to the particulate systems, resulting in improved biological responses.…”

Section: Discussionmentioning

confidence: 99%

Polymer particles that switch shape in response to a stimulus

Yoo

Mitragotri²

2010

Proc. Natl. Acad. Sci. U.S.A.

237

199

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Particle engineering for biomedical applications has unfolded the roles of attributes such as size, surface chemistry, and shape for modulating particle interactions with cells. Recently, dynamic manipulation of such key properties has gained attention in view of the need to precisely control particle interaction with cells. With increasing recognition of the pivotal role of particle shape in determining their biomedical applications, we report on polymeric particles that are able to switch their shape in real time in a stimulusresponsive manner. The shape-switching behavior was driven by a subtle balance between polymer viscosity and interfacial tension. The balance between the two forces was modulated by application of an external stimulus chosen from temperature, pH, or chemical additives. The dynamics of shape switch was precisely controlled over minutes to days under physiological conditions. Shapeswitching particles exhibited unique interactions with cells. Elliptical disk-shaped particles that are not phagocytosed by macrophages were made to internalize through shape switch, demonstrating the ability of shape-switchable particles in modulating interaction with cells.drug delivery | carrier | geometry | nanotechnology | phagocytosis I nteractions of polymeric particles with various cells, including macrophages, in the form of endocytosis and phagocytosis determine the effectiveness of carriers used for drug delivery and medical imaging (1, 2). The outcome of these interactions relies on optimal selection of key particle properties including surface chemistry, size, and shape (3, 4). Accordingly, numerous studies have reported on methods to synthesize materials with precisely engineered functional attributes such as size, surface chemistry, mechanical properties, and shape to facilitate or mitigate interactions with various cell types (3-5).For a given application, particle properties are optimized through extensive experimentation, and a set of fixed values are then chosen for further development. In reality, however, the optimal values of parameters may vary with time depending on the application. This variation has motivated the need to gain dynamic control over key particle properties so as to achieve an interactive interface between the particles and the complex biological milieu. For example, studies have reported on stimulusresponsive type control over the size of particles, and such particles have been used for the triggered release of encapsulated drugs (6-8). In another study, the surface chemistry of polymeric micelles has been controlled by using the environmental pH of solid tumors so as to enhance the cellular uptake and release of anticancer agents (9). Studies have also reported on achieving dynamic control of surface properties through the use of electric fields (10). Relatively little attention, however, has been devoted to switching particle's shape.Here we report poly(lactide-co-glycolide) (PLGA) particles whose shape can be switched in real time from an elliptical disk to a sphere in re...

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Section: Discussionmentioning

confidence: 99%

Polymer particles that switch shape in response to a stimulus

Yoo

Mitragotri²

2010

Proc. Natl. Acad. Sci. U.S.A.

237

199

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“…The influence of carrier deformability on their functionality in flow points to the idea of shape-adaptive carriers that are able to dynamically configure their overall morphology to respond to their local vascular environment in a manner similar to RBCs. As mentioned previously, a PEG coating is commonly used for enhancing circulation half-life and minimizes RES clearance by masking the carrier with a hydration stealth layer (47).…”

Section: Next-generation Vcs: ''Shape-adaptive'' Designmentioning

confidence: 99%

Novel platforms for vascular carriers with controlled geometry

et al. 2011

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SummaryThe first-generation platforms for vascular drug delivery adopted spherical morphologies. These carriers relied primarily on the size dependence of the enhanced permeability and retention effect to passively target vasculature, resulting in inefficient delivery due to significant variation in endothelial permeability. Enhanced delivery typically requires active targeting via receptor-mediated endocytosis by surface conjugation of targeting ligands. However, vascular carriers (VCs) still face numerous challenges en route to reaching their targets before delivery. The control of carrier shape offers opportunities to overcome in vivo barriers and enhance vascular drug delivery. Geometric features influence the ability of carrier particles to navigate physiological flow patterns, evade biological clearance mechanisms, sustain circulation, adhere to the vascular surface, and finally transport across or internalize into the endothelium. Although previous formulation strategies limited the fabrication of nonspherical carriers, numerous recent advances in both top-down and bottom-up fabrication techniques have enabled shape modulation as a key design element. As part of a series on vascular drug delivery, this review focuses on recent developments in novel vascular platforms with controlled geometry that enhance or modulate delivery functions. Starting with an overview of controlled geometry platforms, we review their shape-dependent functional characteristics for each stage of their vascular journey in vivo. We sequentially explore carrier geometries that evade reticuloendothelial system uptake, display enhanced circulation persistence and margination dynamics in flow, encourage adhesion to the vascular surface or extravasation through endothelium, and impact extravascular transport and cell internalization. The eventual biodistribution of VCs results from the culmination of their successive navigation of all these barriers and is profoundly influenced by their morphology. To enhance delivery efficacy, carrier designs synergistically combining controlled geometry with standard drug delivery strategies such as targeting moieties, surface decorations, and bulk material properties are discussed. Finally, we speculate on possibilities for innovation, harnessing shape as a design parameter for the next generation of vascular drug delivery platforms.

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“…Such amphiphilic polymers form in water solution micelle-like structures (MLS) [28] or vesicles [35]. The architecture and functionality of grafted side branches, as well as the grafting degree cause a direct influence on the parameters and morphology of selforganized colloidal structures formed by the molecules of functional comb-like polymeric surfactants in solution [17,28,32,36,37].…”

Section: Introductionmentioning

confidence: 99%