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.
a b s t r a c tWe report a nanocarrier based on A 2 B type miktoarm polymers (A ¼ polyethylene glycol (PEG); B ¼ polycaprolactone (PCL)) for nimodipine (NIM), a hydrophobic drug with very poor aqueous solubility that is commonly prescribed for the prevention and treatment of delayed ischemic neurological disorders. The A 2 B star polymers were constructed on a core with orthogonal functionalities that facilitated the performance of "click" chemistry followed by ring-opening polymerization. These star polymers assemble into spherical micelles into which NIM can be easily loaded by the co-solvent evaporation method. The micelles obtained from the star polymer PEG775 2 ePCL5800 showed NIM encapsulation efficiency of up to 78 wt% at a feed weight ratio of 5.0%. The loading efficiency of the micelles was dependent on the length of the PCL arm in the A 2 B miktoarm polymers. Aqueous solubility of NIM was increased by w200 fold via micellar encapsulation. The in vitro release of NIM from the micelles was found to occur at a much slower rate than from its solution. Lipopolysaccharide induced nitric oxide production in N9 microglia cells was reduced in the presence of micelle-encapsulated NIM, as well as in the presence of micelles alone. The treatment of microglia with micelle-encapsulated NIM reduced the release of TNF-a, a pro-inflammatory cytokine. These results suggest that NIM-loaded miktoarm micelles could be useful in the treatment of neuroinflammation.
A series of neutral pyridyl adducts involving the strong Lewis acids BF 3 and B(C 6 F 5 ) 3 has been prepared, and their second-order nonlinear optical coefficients (EFISH method) have been examined. The formation of the pyridyl-boron bond leads to enhancement of the dipole moments and second-order NLO coefficients (β and β(0)). Reactions of DMAP (4-Me 2 N-C 5 H 4 N) with BH 3 , BF 3 , and B(C 6 F 5 ) 3 give the corresponding neutral pyridine adducts DMAP‚-BH 3 (orthorhombic, Pbca, a ) 9.6914(7) Å; b ) 11.7173(9) Å; c ) 22.718(2) Å; V ) 1622.4(5) Å 3 ; Z ) 8; p ) 1.114 g cm -3 ), DMAP‚BF 3 (orthorhombic, Pbca, a ) 10.430(3) Å; b ) 8.111(2) Å; c ) 20.295(7) Å; V ) 1717.0(9) Å 3 ; Z ) 8; p ) 1.470 g cm -3 ), and DMAP‚B(C 6 F 5 ) 3 (orthorhombic, Pbca, a ) 12.322(1) Å; b ) 20.556(2) Å; c ) 28.455(3) Å; V ) 7207.4(14) Å 3 ; Z ) 8; p ) 1.508 g cm -3 ). Reactions of Me 2 N-4-C 6 H 4 -CHdCH-C 5 H 4 N, MeO-4-C 6 H 4 -CHdCH-C 5 H 4 N, and Me 2 N-4-C 6 H 4 -CtC-C 5 H 4 N with BF 3 and B(C 6 F 5 ) 3 result in materials that are highly luminescent and incorporate structural features that are known to give rise to large second-order NLO effects. X-ray diffraction analysis for the compound Me 2 N-4-C 6 H 4 -CtC-C 5 H 4 N‚B(C 6 F 5 ) 3 (monclinic, P2 1 /c, a ) 9.883(2) Å; b ) 10.717(1) Å; c ) 28.421-(4) Å; β ) 91.96(1)°; V ) 2993.4(8) Å 3 ; Z ) 4; p ) 1.629 g cm -3 ) is also described.
The delivery of biologically active agents to the desired site in the body and intracellular organelles is still a big challenge despite efforts made for more than five decades. With the elaboration of synthetic methodologies to branched and hyperbranched macromolecules such as miktoarm stars and dendrimers, the focus has shifted to nanocarriers able to release and direct drug molecules to a desired location in a controlled manner. We present here recent developments in the field of targeted drug delivery with a focus on two specific macromolecular nanocarriers, dendrimers and miktoarm stars, and provide examples of these nanocarriers tested in different biological systems. A particular attraction of miktoarm stars is their versatility in achieving superior drug loading within their self-assembled structures. Advantages of dendrimers over linear polymers are that the former provide a platform for development of multivalent and multifunctional nanoconjugates, in addition to their ability to accommodate a large number of molecules inside, or at their surfaces.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.