Particle shape: a new design parameter for micro- and nanoscale drug delivery carriers

Abstract

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.

Figure 1

(A) Plug-shaped particle made of optical adhesive polymer by Dendukuri et al. with microfluidics [27]. (B) Toroidal PS particles prepared via self-assembly by Velev et al. (scale 500 µm) [31]. (C) PS vase-shaped particle made Sozzani et al. by direct replication (scale 1 µm) [30]. (D) PolyTPGDA rods made by Xu et al. with microfluidics [26]. (E) Curved PEG particle made by Dendukuri et al. via microscope projection photolithography (scale 10 µm) [28]. (F) Conical PEG particles made by Rolland et al. with a non-wetting mold [29].

Figure 2

(A) Double layered zigzag chain made by Yin et al. with 4.3 µm PS beads by template-assisted self-assembly [33]. (B) Pentagonal bipyramid containing seven 844 nm PS particles self-assembled by Manoharan et al. [32]. (C) Ellipsoidal PS particles stretched by Ho et al. from 208 nm spheres [34].

Figure 3

Scanning electron micrographs of polystyrene particles created by stretching method: (A) oblate ellipsoids, (B) prolate ellipsoids, (C) elliptical disks and (D) UFOs [35]. Scale bars = 5 µm.

Figure 4

Scanning electron micrograph of poly(lactic acid-co-glycolic acid) elliptical disks created by film stretching method. Polydispersity in size is due to polydispersity in original spherical particles. Scale bar = 1 µm.

Figure 5

Colored scanning electron micrographs of alveolar macrophages (brown) interacting with PS particles (purple). (A) The cell body can be seen at the end of an opsonized elliptical disk and the membrane has progressed down the length of the particle. Scale bar = 10 µm. (B) A cell has attached to the flat side of an opsonized elliptical disk and has spread on the particle. Scale bar = 5 µm. (C) An opsonized spherical particle has attached to the top of a cell and the membrane has progressed over approximately half the particle. Scale bar = 5 µm.