PEGylated PRINT Nanoparticles: The Impact of PEG Density on Protein Binding, Macrophage Association, Biodistribution, and Pharmacokinetics

In this account, we varied PEGylation density on the surface of hydrogel PRINT nanoparticles and systematically observed the effects on protein adsorption, macrophage uptake, and circulation time. Interestingly, the density of PEGylation necessary to promote a long-circulating particle was dramatically less than what has been previously reported. Overall, our methodology provides a rapid screening technique to predict particle behavior in vivo and our results deliver further insight to what PEG density is necessary to facilitate long-circulation

Scalable Manufacture of Built-to-Order Nanomedicine: Spray-Assisted Layer-by-Layer Functionalization of PRINT Nanoparticles

Scalable methods, PRINT particle fabrication, and spray-assisted Layer-by-Layer deposition are combined to generate uniform and functional nanotechnologies with precise control over composition, size, shape, and surface functionality. A modular and tunable approach towards design of built-to-order nanoparticle systems, spray coating on PRINT particles is demonstrated to achieve technologies capable of targeted interactions with cancer cells for applications in drug delivery.National Cancer Institute (U.S.) (Center for Cancer Nanotechnology Excellence Grant 5 U54 CA151884-02)National Science Foundation (U.S.). Graduate Research FellowshipNatural Sciences and Engineering Research Council of Canada (Postdoctoral Fellowship

Top-Down Particle Fabrication: Control of Size and Shape for Diagnostic Imaging and Drug Delivery

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

PRINT: A Novel Platform Toward Shape and Size Specific Nanoparticle Theranostics

Nanotheranostics represents the next generation of medicine, fusing nanotechnology, therapeutics, and diagnostics. By integrating therapeutic and imaging agents into one nanoparticle, this new treatment strategy has the potential not only to detect and diagnose disease but also to treat and monitor the therapeutic response. This capability could have a profound impact in both the research setting as well as in a clinical setting. In the research setting, such a capability will allow research scientists to rapidly assess the performance of new therapeutics in an effort to iterate their designs for increased therapeutic index and efficacy. In the clinical setting, theranostics offers the ability to determine whether patients enrolling in clinical trials are responding, or are expected to respond, to a given therapy based on the hypothesis associated with the biological mechanisms being tested. If not, patients can be more quickly removed from the clinical trial and shifted to other therapeutic options. To be effective, these theranostic agents must be highly site specific. Optimally, they will carry relevant cargo, demonstrate controlled release of that cargo, and include imaging probes with a high signal-to-noise ratio

Scalable, Shape-Specific, Top-Down Fabrication Methods for the Synthesis of Engineered Colloidal Particles

The search for a method to fabricate non-spherical colloidal particles from a variety of materials is of growing interest. As the commercialization of nanotechnology continues to expand, the ability to translate particle fabrication methods from a laboratory to an industrial scale is of increasing significance. In this article, we examine several of the most readily scalable top-down methods for the fabrication of such shape specific particles and compare their capabilities with respect to particle composition, size, shape and complexity as well as the scalability of the method. We offer an extensive examination of Particle Replication In Non-wetting Templates (PRINT®) with regards to the versatility and scalability of this technique. We also detail the specific methods used in PRINT particle fabrication, including harvesting, purification and surface modification techniques, with examination of both past and current methods

Kinetic Studies on the Effect of Acidity and Temperature on the Loss of Optical Activity of Some Butanediols

In aqueous perchloric acid, butane-1, 2-diol (1) and butane-2, 3-diol (2) give carbonyls and butane-1, 3-diol (3) gives alkenols. The rate of loss of optical activity has been determined for these diols and butan-2-ol (4) over a range of temperatures and acidities. In 1 m acid at 100°C, the rates for (1), (2), (3) and (4) are in the ratio of 1: 2·3: 3·7: 45 respectively. The activation parameters are similar for all the alcohols. Hammett acidity plots give slopes of c. 0·8 for the diols and of 1 for butan-2-ol. These variations in these kinetic parameters are discussed in terms of whether hydroxyl group substitution in butan-2-ol affects the mechanism of its reaction in these circumstances

Kinetics of the pinacol rearrangement of propane-1, 2-diol

The pinacol rearrangement of propane-1, 2-diol in aqueous acid gives propanal. The rate of loss of optical activity (k) is greater than the loss of diol (k) over the range of acid concentrations investigated. Also the ratio kk decreases with the increasing acidity. A value of c. 0·5 has been obtained for the relative rates of oxygen exchange to racemization. Relative rates for the partitioning of a proposed carbocation intermediate have been calculated from these data

PEGylated PRINT Nanoparticles: The Impact of PEG Density on Protein Binding, Macrophage Association, Biodistribution, and Pharmacokinetics

In this account, we varied PEGylation density on the surface of hydrogel PRINT nanoparticles and systematically observed the effects on protein adsorption, macrophage uptake, and circulation time. Interestingly, the density of PEGylation necessary to promote a long-circulating particle was dramatically less than what has been previously reported. Overall, our methodology provides a rapid screening technique to predict particle behavior in vivo and our results deliver further insight to what PEG density is necessary to facilitate long-circulation