Miktoarm polymers are a relatively new and unique class of macromolecules, and constitute a topical area of research due to their intriguing properties which can be tailored by varying their polymer arms. Much emphasis has been placed in the recent past in developing synthetic methodologies to these star polymers, and examining their self-assembly in solution. This review summarizes the progress made in the area of miktoarm star polymers in terms of their synthesis, behavior in solution, and applications. The different synthetic strategies to construct a variety of miktoarm star polymers are described, and each methodology strikes a balance between ease of synthesis and control over the final architecture. The self-assembly of miktoarm polymers in solution is then elaborated, which is frequently studied as a function of either arm-length (an intrinsic property of the star) or the application of an external stimulus (pH, temperature, etc.). This is followed by an overview of the applications of these stars in areas including drug delivery.
Designing therapeutics is a process with many challenges. Even if the first hurdle — designing a drug that modulates the action of a particular biological target in vitro — is overcome, selective delivery to that target in vivo presents a major barrier. Side-effects can, in many cases, result from the need to use higher doses without targeted delivery. However, the established use of macromolecules to encapsulate or conjugate drugs can provide improved delivery, and stands to enable better therapeutic outcomes. In this Review, we discuss how drug delivery approaches have evolved alongside our ability to prepare increasingly complex macromolecular architectures. We examine how this increased complexity has overcome the challenges of drug delivery and discuss its potential for fulfilling unmet needs in nanomedicine.
Despite the possible role of impaired cerebral tissue oxygenation in age-related cognition decline, much is still unknown about the changes in brain tissue pO2 with age. Using a detailed investigation of the age-related changes in cerebral tissue oxygenation in the barrel cortex of healthy, awake aged mice, we demonstrate decreased arteriolar and tissue pO2 with age. These changes are exacerbated after middle-age. We further uncovered evidence of the presence of hypoxic micro-pockets in the cortex of awake old mice. Our data suggests that from young to middle-age, a well-regulated capillary oxygen supply maintains the oxygen availability in cerebral tissue, despite decreased tissue pO2 next to arterioles. After middle-age, due to decreased hematocrit, reduced capillary density and higher capillary transit time heterogeneity, the capillary network fails to compensate for larger decreases in arterial pO2. The substantial decrease in brain tissue pO2, and the presence of hypoxic micro-pockets after middle-age are of significant importance, as these factors may be related to cognitive decline in elderly people.
Designing dendrimers that are monodisperse hyperbranched macromolecules and offer significant potential in numerous scientific fields, is becoming a major topical area in modern research. Among the challenges of the 21st century, synthetic methodologies that increase efficiency of conversion and a greener chemistry approach, are expected to lead the way in the quest to build novel nanomaterials. The recent entry of so-called "click" reactions that include Diels-Alder, Cu(I)-catalyzed Huisgen cycloaddition and thiol-ene coupling, have generated real stimulus not only in developing elegant materials of choice, but also in making the leap to industrial scale build-up of dendritic macromolecules. This tutorial review takes on the task of demonstrating the simplicity of these "click" reactions and the advantages they offer from a synthetic view point in developing mono- to multifunctional dendrimers. A brief introduction to "click" chemistry is followed by a chronological survey of developments in the field, and the impact these have had in designing novel dendritic macromolecules. The review is intended to introduce scientists to these highly efficient methodologies with demonstrated potential, and provide impetus for further growth of the area.
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