In Drug Delivery, Shape Does Matter
- First Online:
- Cite this article as:
- Mitragotri, S. Pharm Res (2009) 26: 232. doi:10.1007/s11095-008-9740-y
- 537 Views
Design and engineering of novel carriers for drug delivery has long been an area of active research (1). Numerous studies have been reported on engineering carriers for encapsulation of drugs, release, biocompatibility, clearance, and targeting. Researchers have long sought to define key design parameters that govern the performance of drug delivery carriers. Two parameters in particular, size and surface chemistry have been extensively studied. Several general guidelines have been established to guide the selection of size and surface chemistry to achieve the desired response. For example, nanoparticles with diameters less than 100 nm are considered suitable for tumor targeting via leaky vasculature (2). On the other hand, large microspheres (d > 40 μm) have been used as embolizing agents. Various guiding principles have also been established for selection of surface chemistry. For example, immobilization of polyethylene glycol on particles has been shown to reduce protein adsorption and phagocytosis (3). On the other hand, immobilization of peptides has been used to target particles to various organs (4). Optimization of surface coating for balancing stealth vs. targeting properties has also been reported (5).
In the last few years, however, there has been growing recognition that particle properties other than size and surface chemistry can be engineered for the purpose of drug delivery (6–9). Among them, shape represents an important particle parameter. There already exist several examples of how shape of carriers can be controlled to enhance the performance of drug delivery carriers. Recent studies performed using particles of different shapes have shown that phagocytosis by macrophages exhibits a strong dependence on shape (10). At a smaller length scale, Gratton et al. demonstrated that internalization of cylindrical particles exhibits a strong dependence on their aspect ratio. Specifically, particles with an aspect ratio of three were internalized about four times faster than their spherical counterparts of the same volumes (11). Counter examples of dependence of internalization on shape also exist (8). It is possible that the precise dependence of internalization on shape depends on the interplay between several other parameters. Particle shape has also been shown to influence carrier behavior in vivo. Specifically, Geng et al. (8) have shown that long cylindrical micelles exhibit long circulation and high tumor targeting compared to their spherical counterparts. More recently, Muro et al. (9) compared biodistribution of spherical and disk-shaped particles and reported that large elliptical disks exhibited higher targeting efficiency compared to spheres. One thing is clear; shape has a profound impact on performance of drug carriers.
This theme issue is dedicated to the role of carrier shape in drug delivery. Three contributions describe various aspects of the role of shape in drug delivery. The first manuscript by Champion and Mitragotri reports the impact of shape on phagocytosis. Specifically, they report that long, worm-shaped particles exhibit negligible phagocytosis compared to spherical particles of equal volume. The authors suggest that reduced phagocytosis is a result of decreasing high curvature regions of the particle to two single points, the ends of the worm-shaped particles. The second contribution by Gratton et al. reports on endocytosis of shape- and size-specific particles as a function of zeta potential in different cell types. Using a top-down particle fabrication technique called PRINT, the authors fabricate monodisperse 1 µm cylindrical particles and report that cylindrical 1 μm particles are readily internalized into various cells without toxicity. The third contribution analyzes the role of particle geometry (size and shape) at the tissue and cellular scale. Decuzzi and Ferrari compare predictions of mathematical models and observations from in vitro experiments to show the relevance of particle geometry in systemic delivery.
The field of “shape engineering” of drug delivery carriers is still in its infancy. However, the existing literature on this topic, regardless of its small size, clearly indicates the merits of exploring shape as an important parameter and hints at the exciting prospects of this field.