Encapsulation of therapeutic agents in polymer particles has been successfully used in the development of new drug carriers. A number of design parameters that govern the functional behavior of carriers, including the choice of polymer, particle size and surface chemistry, have been tuned to optimize their performance in vivo. However, particle shape, which may also have a strong impact on carrier performance, has not been thoroughly investigated. This is perhaps due to the limited availability of techniques to produce non-spherical polymer particles. In recent years, a number of reports have emerged to directly address this bottleneck and initial studies have indeed confirmed that particle shape can significantly impact the performance of polymer drug carriers. This article provides a review of this field with respect to methods of particle preparation and the role of particle shape in drug delivery.

Polymeric micro-and nanoparticles play a central role in varied applications such as drug delivery, medical imaging, and advanced materials, as well as in fundamental studies in fields such as microfluidics and nanotechnology. Functional behavior of polymeric particles in these fields is strongly influenced by their shape. However, the availability of precisely shaped polymeric particles has been a major bottleneck in understanding and capitalizing on the role of shape in particle function. Here we report a method that directly addresses this need. Our method uses routine laboratory chemicals and equipment to make particles with >20 distinct shapes and characteristic features ranging in size from 60 nm to 30 m. This method offers independent control over important particle properties such as size and shape, which is crucial to the development of nonspherical particles both as tools and products for a variety of fields.morphology ͉ nanotechnology ͉ geometry ͉ drug delivery ͉ nonspherical P olymeric particles are used in a diverse array of applications including drug delivery (1), advanced materials (2), personal care (3), and medical imaging (4). They also are used in fundamental studies in fields such as microfluidics (5) and nanotechnology (6). Particle shape is a critical parameter that can significantly influence particle function. The vast potential of shape, however, has not been fully explored due to difficulties in creating polymer particles with controlled shapes. Several reports exist on fabrication of polymeric particles with nonspherical geometries. These approaches make use of self-assembly (7-9), photolithography (10), nonwetting template molding (11), microfluidics (12, 13), and stretching of spherical particles (14,15). Collectively, these methods have produced particles of several distinct shapes. Some of these methods provide advantages such as scalability, high throughput, and precise control over particle shape. However, they also suffer from drawbacks including cost, particle size limitations, low throughput, and limited ability to sculpt particles in three dimensions. Accordingly, simple, versatile, inexpensive, and high-throughput methods of fabricating nonspherical particles still remain a bottleneck of future discoveries in a diverse array of fields. Here, we report a simple method that generates particles of Ͼ20 distinct shapes in large, reproducible quantities. ResultsSpherical polystyrene (PS) particles of diameters between 60 nm and 10 m are used here as a starting material for preparing particles of complex shapes. These particles are suspended in an aqueous solution of polyvinyl alcohol (PVA) and cast into films (14), which are then manipulated to engineer particle shape. The method for engineering shape can be classified into two general approaches (Fig. 1). In the first approach, termed scheme A, PS particles are liquefied by using solvent or by heating above the glass transition temperature (T g ) of PS and then stretched in one or two dimensions. In the second approach, scheme B...

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