Top‐down particle fabrication: control of size and shape for diagnostic imaging and drug delivery

Abstract

This review discusses rational design of particles for use as therapeutic vectors and diagnostic imaging agent carriers. The emerging importance of both particle size and shape is considered, and the adaptation and modification of soft lithography methods to produce nanoparticles is highlighted. To this end, studies utilizing particles made via a process called Particle Replication In Non-wetting Templates (PRINT ™ ) are discussed. In addition, insights gained into therapeutic cargo and imaging agent delivery from related types of polymer-based carriers are considered. KeywordsPRINT; nanoparticles; diagnostic imaging; therapeutic drug delivery; shape With rapid development of new pharmaceuticals and contrast agents, the need for the minimization of side effects in concert with simultaneous targeted delivery to specific tissues of interest continues to expand. Overcoming barriers for effective bioavailability of therapeutic agents has been especially challenging in the fields of gene therapy[1] and oncology. [2] As an illustration, despite their potential for wide application, only a few antisense oligonucleotides or small interfering RNA's (siRNA) have entered clinical trials. The prevalence of hydrophobic drugs also necessitates the use of nanocarriers; for these systems, direct dissolution in the bloodstream is limited without the formation of a salt or use of a delivery vector. [3] One solution to this problem is the delivery of drugs, gene therapy agents, and imaging contrast agents via nano-scale vectors, and this has been an area of intense study for decades. Although multiple approaches have been explored and strides have been made in therapeutic drug delivery and diagnostic imaging agent carriers, a set of rules for the rational design of nanocarriers has not yet been fully established due to limited understanding of how all of the carrier properties (including size and shape as well as matrix Cross-References MR relaxation properties of superparamagnetic iron oxide particles Microlithographic delivery devices Nano-encapsulation technology to deliver native protein drugs NIH Public Access Author ManuscriptWiley Interdiscip Rev Nanomed Nanobiotechnol. Author manuscript; available in PMC 2010 July 1. Published in final edited form as:Wiley Interdiscip Rev Nanomed Nanobiotechnol. Rational Design of Drug and Contrast Agent CarriersSeveral critical factors that must be considered in the design of contrast agent and/or polymeric drug carriers include the chemical functionality and mechanical flexibility of the matrix, the degree of cross-linking, if any, the dispersion or encapsulation of the drug within the matrix, the permeability of the cargo through the matrix of the particle, the number and the nature of phases that comprise the particle (one phase versus two or more phases e. g. drug rich phase and matrix rich phase,) the size and shape of the particle, and the surface chemistry. Many of these factors need to be studied and controlled in particle design for the delivery of imaging contrast agent...

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