Nanofabricated particles for engineered drug therapies: A preliminary biodistribution study of PRINT™ nanoparticles

Abstract

A novel method for the fabrication of polymeric particles on the order of tens of nanometers to several microns is described. This imprint lithographic technique called PRINT™ (Particle Replication In Non-wetting Templates), takes advantage of the unique properties of elastomeric molds comprised of a low surface energy perfluoropolyether network, allowing the production of monodisperse, shapespecific nanoparticles from an extensive array of organic precursors. This engineered nature of particle production has a number of advantages over the construction of traditional nanoparticles such as liposomes, dendrimers, and colloidal precipitates. The gentle "top down" approach of PRINT enables the simultaneous and independent control over particle size and shape, composition, and surface functionality, and permits the loading of delicate cargos such as small organic therapeutics and biological macromolecules. Thus, this single tool serves as a comprehensive platform for the rational design and investigation of new nanocarriers in medicine, having applications ranging from therapeutics to advanced diagnostics. Preliminary in vitro and in vivo studies were conducted, demonstrating the future utility of PRINT particles as delivery vectors in nanomedicine. Monodisperse 200 nm poly(ethylene glycol)-based (PEG) particles were fabricated using PRINT methodology and characterized via scanning electron microscopy and dynamic light scattering. Incubation with HeLa cells showed very little cytotoxicity, even at high concentrations. The biodistribution and pharmacokinetics of [ 125 I]-labeled particles were studied in healthy mice following bolus tail vein administration. The particles were distributed mainly to the liver and the spleen with an apparent distribution t 1/2 of approximately 17 min followed by slow redistribution with a t 1/2 of 3.3 h. The volume of distribution for the central and peripheral compartments was found to be approximately 3 mL and 5 mL, respectively.

Using shape effects to target antibody-coated nanoparticles to lung and brain endothelium

“…Greater specific attachment exhibited by rod-shaped particles offers several advantages in the field of drug delivery, particularly in the delivery of drugs such as chemotherapeutics, which are highly toxic and necessitate the use of targeted approaches. The benefits of elongated particles in drug delivery were reported previously, and techniques for the mass production of different-shaped particles are being developed (40,41). At a micrometer scale, studies have shown that elongated particles exhibit reduced phagocytosis (28,42) and exhibit increased accumulation in lungs (22).…”

The effect of particle design on cellular internalization pathways

“…We designed a series of particles with varying sizes and shapes at a constant chemical composition (i.e., at a constant surface charge) by using a top-down lithographic fabrication method called PRINT (Particle Replication In Non-wetting Templates) (17)(18)(19). The PRINT micro-and nanoparticles were made from cationic, cross-linked poly(ethylene glycol) hydrogels and were designed to study the interdependent effect of size, shape, and surface charge (zeta potential) on their internalization by human cervical carcinoma epithelial (HeLa) cells.…”

Monodisperse, Shape-Specific Nanobiomaterials for Cancer Therapeutics and Imaging Agents

“…[1][2][3] PRINT is a remarkable top-down particle fabrication technique that has its roots in high resolution imprint lithography, an emerging technique from the microelectronics industry and is a direct result of the discovery of a unique liquid perfl uoropolyether that allows the fabrication of precisely defi ned nanoparticles with control over size, shape, composition, cargo, deformability and surface chemistry. Th e PRINT process, shown in Figure 1, begins with the fabrication of a master template using advanced lithographic techniques.…”

“…Our laboratory has pioneered the development of a technique called PRINT (Particle Replication in Non-wetting Templates). [1][2][3] PRINT is a remarkable top-down particle fabrication technique that has its roots in the manufacturing and fabrication processes used in the microelectronics industry to make transistors. PRINT is a high resolution molding technique that allows for the fabrication of precisely defi ned nanoparticles with control over size, shape, deformability and surface chemistry.…”