Abstract
The storied history of controlled the release systems has evolved over time; from degradable drug-loaded sutures to monolithic zero-ordered release devices and nano-sized drug delivery formulations. Scientists have tuned the physico-chemical properties of these drug carriers to optimize their performance in biomedical/pharmaceutical applications. In particular, particle drug delivery systems at the micron size regime have been used since the 1980s. Recent advances in micro and nanofabrication techniques have enabled precise control of particle size and geometry–here we review the utility of microplates and discoidal polymeric particles for a range of pharmaceutical applications. Microplates are defined as micrometer scale polymeric local depot devices in cuboid form, while discoidal polymeric nanoconstructs are disk-shaped polymeric particles having a cross-sectional diameter in the micrometer range and a thickness in the hundreds of nanometer range. These versatile particles can be used to treat several pathologies such as cancer, inflammatory diseases and vascular diseases, by leveraging their size, shape, physical properties (e.g., stiffness), and component materials, to tune their functionality. This review highlights design and fabrication strategies for these particles, discusses their applications, and elaborates on emerging trends for their use in formulations.Graphical abstract
Highlights
Microplates and discoidal polymeric nanoparticles as controlled release systems The well-known history of controlled release can be traced back to the 1950s and 1960s [1, 2], and since the turn of the millenium the focus has been on developing particle drug delivery systems on the nanoscale
Non-spherical nano- and microparticles have been proposed recently as an alternative system for systemic and local drug delivery to treat a variety of pathologies [10–16], and advances in nano- and microfabrication techniques have enabled the fine tuning of particle’s size and geometry with a great impact on how such particles interact with the surrounding environment, as well as on the modulation of the drug release profile
Overviews of two specific “micro” drug delivery systems are presented–microplates and discoidal polymeric nanoconstructs (DPNs) for a range of pharmaceutical applications. μPLs (Fig. 1B) are micron-sized, square polymeric particles that act as a local therapeutic depot [10, 11], while DPNs (Fig. 1C) are disk-shaped polymeric particles with a cross-sectional diameter in the micrometer range, a thickness in the hundreds of nanometer range, and are intended for a systemic administration [12–14]
Summary
In order to tailor the physiochemical properties of particlebased drug delivery systems to the desired administration route and pathology, a variety of top-down or bottom-up methods can be employed (Table 1). Particles are photopolymerized under flow with a mask that can yield controlled geometries have become more accessible to researchers over the past decade [20–24] These approaches rely on the a priori definition of the physical features of such particles, to more common self-assembly fabrication techniques (bottomup approaches), whose outcome is very often spherical. Dissolving the PVA template yields highly uniform particles of the desired geometries and sizes, and loading of therapeutics can be achieved in the same step as polymer particle formation by including drug molecules in the precursor solutions (Fig. 1). This developed process for size- and shape-defined particles offers many advantages. One of the challenges of these top-down particle fabrication technologies is that scaling templatebased methods to industrial levels requires considerable process development expertise or potentially redesign to fit roll-to-roll or continuous-flow techniques
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