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Abstract The paper presents the results of the experimental and analytical study of targeted drug-loaded polymer-based microspheres made from blend polymer of polylactic-co-glycolic acid and polycaprolactone (PLGA-PCL) for targeted and localized cancer drug delivery. In vitro sustained release with detailed thermodynamically driven drug release kinetics, over a period of three months using encapsulated targeted drugs (prodigiosin-EphA2 or paclitaxel-EphA2) and control drugs [Prodigiosin (PGS), and paclitaxel (PTX)] were studied. Results from in vitro study showed a sustained and localized drug release that is well-characterized by non-Fickian Korsmeyer–Peppas kinetics model over the range of temperatures of 37 °C (body temperature), 41 °C, and 44 °C (hyperthermic temperatures). The in vitro alamar blue, and flow cytometry assays in the presence of the different drug-loaded polymer formulations resulted to cell death and cytotoxicity that was evidence through cell inhibition and late apoptosis on triple negative breast cancer (TNBC) cells (MDA-MB 231). In vivo studies carried out on groups of 4-week-old athymic nude mice that were induced with subcutaneous TNBC, showed that the localized release of the EphA2-conjugated drugs was effective in complete elimination of residual tumor after local surgical resection. Finally, ex vivo histopathological analysis carried out on the euthanized mice revealed no cytotoxicity and absence of breast cancer metastases in the liver, kidney, and lungs 12 weeks after treatment. The implications of the results are then discussed for the development of encapsulated EphA2-conjugated drugs formulation in the specific targeting, localized, and sustain drug release for the elimination of local recurred TNBC tumors after surgical resection. Graphical Abstract

Presumptive drug screening enables timely procurement of search and arrest warrants and represents a crucial first step in crime scene analysis. Screening also reduces the burden on forensic laboratories which often face insurmountable backlogs. In most scenarios, on-site presumptive drug screening relies on chemical field tests for initial identification. However, even when used appropriately, these test kits remain limited to subjective colorimetric analysis, produce false positive or negative results with excessive sample quantities, and are known to cross-react with numerous innocuous substances. Previous efforts to develop microfluidic devices that incorporate these chromogenic indicator reagents address only a few of the many challenges associated with these kits. This is especially true for samples where the drug of interest is present as a lacing agent. This work describes the development of a centrifugal microfluidic device capable of integrating facile sample preparation, by way of a 3D printed snap-on cartridge amenable to microwave assisted extraction, followed by chromatographic separation and chromogenic detection on-disc. As cannabis is among the most widely used controlled substance worldwide, and displays strong interference with these indicator reagents, mock samples of laced marijuana are used for a proof-of-concept demonstration. Post extraction, the microdevice completes high throughput metering just prior to simultaneous reaction with four of the most commonly employed microchemical tests, followed by objective image analysis in CIELAB (a device-independent color model). Separation and recovery of a representative controlled substance with 93% efficiency is achieved. Correct identification, according to hierarchical cluster analysis, of three illicit drugs (e.g., heroin, phencyclidine, and cocaine) in artificially laced samples is also demonstrated on-disc. The cost effective microdevice is capable of complete automation post-extraction, with a total analysis time (including extraction) of <8 min. Finally, sample consumption is minimized, thereby preventing the complete destruction of forensic evidence. [ABSTRACT FROM AUTHOR]

Methods for reducing the radius, temperature and space charge of a non-neutral plasma are usually reported for conditions which approximate an ideal Penning Malmberg trap. Here, we show that (i) similar methods are still effective under surprisingly adverse circumstances: we perform strong drive regime (SDR) compression and SDREVC in a strong magnetic mirror field using only 3 out of 4 rotating wall petals. In addition, we demonstrate (ii) an alternative to SDREVC, using e-kick instead of evaporative cooling (EVC) and (iii) an upper limit for how much plasma can be cooled to $T using EVC. This limit depends on the space charge, not on the number of particles or the plasma density. [ABSTRACT FROM AUTHOR]

Centrifugal microfluidics has evolved into a sophisticated technology capable of enabling the exploration of fundamental questions in such fields as protein analysis, environmental monitoring, and live cell handling. These microdevices also hold unique potential for translating promising academic research into many real-world scenarios, with several products already available on the market. Yet, in order to fully realize this potentially transformative technology, there remains an outstanding need to incorporate simple to operate world-to-chip interfaces alongside the integration and automation of complex workflows. This requires cost-effective and versatile materials that are, ideally, already commercially available. Membranes not only meet these exigencies, they are also capable of enhancing the inherent advantages of microdevices when thoughtfully combined. This review provides an overview of the importance of these two technologies and the manifold benefits upon their unification. The fundamental principles governing fluid flow with centrifugal actuation, as well as within porous membranes, are briefly covered in addition to a comment on their relative advantages compared to classical microdevices and porous media. The major subtypes in membrane composition, preparation, and microfluidic integration strategies are next discussed in detail, along with their relativistic capabilities and drawbacks. This is followed by recent examples in the literature displaying the enormous versatility membranes have already demonstrated within microfluidic devices, highlighting recent centrifugal microdevices wherever possible. Finally, recommendations for areas where the incorporation of these materials still face challenges, as well as possible new avenues for exploration, are also provided. [ABSTRACT FROM AUTHOR]

This article presents silica nanoparticles for the sustained release of AMACR antibody‐conjugated and free doxorubicin (DOX) for the inhibition of prostate cancer cell growth. Inorganic MCM‐41 silica nanoparticles were synthesized, functionalized with phenylboronic acid groups (MCM‐B), and capped with dextran (MCM‐B‐D). The nanoparticles were then characterized using Fourier‐transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, zeta potential analysis, nitrogen sorption, X‐ray diffraction, and thermogravimetric analysis, before exploring their potential for drug loading and controlled drug release. This was done using a model prostate cancer drug, DOX, and a targeted prostate cancer drug, α‐Methyl Acyl‐CoA racemase (AMACR) antibody‐conjugated DOX, which attaches specifically to AMACR proteins that are overexpressed on the surfaces of prostate cancer cells. The kinetics of sustained drug release over 30 days was then studied using zeroth order, first order, second order, Higuchi, and the Korsmeyer–Peppas models, while the thermodynamics of drug release was elucidated by determining the entropy and enthalpy changes. The flux of the released DOX was also simulated using the COMSOL Multiphysics software package. Generally, the AMACR antibody‐conjugated DOX drug‐loaded nanoparticles were more effective than the free DOX drug‐loaded formulations in inhibiting the growth of prostate cancer cells in vitro over a 96 h period. The implications of the results are then discussed for the development of drug‐eluting structures for the localized and targeted treatment of prostate cancer. [ABSTRACT FROM AUTHOR]

Many assays necessitate the use of highly concentrated acids, powerful oxidizing agents, or a combination of the two. Although microfluidic devices offer vast potential for rapid analytical interrogation at the point-of-need (PON), they cannot escape the fundamental requirement for reagent compatibility. Worse, many innovative protocols have been developed that would represent a significant improvement to current field-forward practices within their respective disciplines, but adoption falters due to chemical incompatibility with challenging reagents. Polymeric centrifugal microfluidic devices meet many of the needs for accommodating complex chemical or biochemical protocols in a multiplexed and automatable format. Yet, they also struggle to accommodate highly reactive chemical components long term. In this work, we report on a simple and inexpensive reagent storage strategy that bypasses the typical complexity involved with integration of liquid reagents on microfluidic devices. Moreover, we demonstrate microdevice compatibility and operation after six months of corrosive reagent storage as well as post dielectric heating. This new strategy allows for storage of multiple highly corrosive and oxidative reagents simultaneously, enhancing the possibilities for multistep assay integration at the PON for a diverse array of applications. Successful detection after one week of corrosive reagent storage of an illicit drug and neurotransmitter metabolite, for forensic and clinical applications, is demonstrated. Furthermore, environmental sample preparation via microwave-assisted wet acid digestion is performed on-disc and integrated with downstream detection. Quantitative detection of a heavy metal in soil is achieved by way of on-disc calibration and found to be accurate within 2.4% compared to a gold standard reference (ICP-OES). [ABSTRACT FROM AUTHOR]

A learning cycle approach to undergraduate instruction implemented in a variety of subjects at Metropolitan State College in Denver is described. An experimental group demonstrated significant gains in critical thinking and cognitive skill development as well as improved retention using a framework based on Piaget's stages of cognitive development. (JMF)

Investigates the cognitive functioning of 106 college freshmen using six paper-pencil Piagetian-based tasks. Results show that only 25 percent of the freshmen tested were reasoning at a formal level. (HM)