Dendrimers are branched, synthetic polymers with layered architectures that show promise in several biomedical applications. By regulating dendrimer synthesis, it is possible to precisely manipulate both their molecular weight and chemical composition, thereby allowing predictable tuning of their biocompatibility and pharmacokinetics. Advances in our understanding of the role of molecular weight and architecture on the in vivo behavior of dendrimers, together with recent progress in the design of biodegradable chemistries, has enabled the application of these branched polymers as anti-viral drugs, tissue repair scaffolds, targeted carriers of chemotherapeutics and optical oxygen sensors. Before such products can reach the market, however, the field must not only address the cost of manufacture and quality control of pharmaceutical-grade materials, but also assess the long-term human and environmental health consequences of dendrimer exposure in vivo.
The antitumor effect of doxorubicin (DOX) conjugated to a biodegradable dendrimer was evaluated in mice bearing C-26 colon carcinomas. An asymmetric biodegradable polyester dendrimer containing 8 -10 wt % DOX was prepared. The design of the dendrimer carrier optimized blood circulation time through size and molecular architecture, drug loading through multiple attachment sites, solubility through PEGylation, and drug release through the use of pH-sensitive hydrazone linkages. In culture, dendrimer-DOX was >10 times less toxic than free DOX toward C-26 colon carcinoma cells after exposure for 72 h. antitumor ͉ molecular architecture ͉ therapeutic effect ͉ nanomedicine ͉ dendrimer prodrug
This tutorial review serves as an introduction to helical self-assembled systems, illustrated by a specific class of helical aggregates: helical nanofibers. The common ways by which these systems are designed, prepared, and characterized will be presented.
A library of polyurethanes and polyureas with different hydrophobicities containing the same acid-degradable dimethyl ketal moiety embedded in the polymer main chain have been prepared. All polymers were synthesized using an AA-BB type step-growth polymerization by reaction of bis(p-nitrophenyl carbamate/carbonate) or diisocyanate monomers with an acid-degradable, ketal-containing diamine. These polymers were designed to hydrolyze at different rates in mildly acidic conditions as a function of their hydrophobicity to afford small molecules only with no polymeric byproduct. The library of polymers was screened for the formation of microparticles using a double emulsion technique. The microparticles that were obtained degraded significantly faster at acidic pH (5.0) than at physiological pH (7.4) with degradation kinetics related to the hydrophobicity of the starting polymer. In vitro studies demonstrated the ability of the FITC-BSA loaded microparticles to be phagocytosed by macrophages resulting in a 10-fold increase in the protein uptake compared to a free protein control; in addition, the microparticles were found to be nontoxic at the concentrations tested of up to 1 mg/mL. The ease of preparation of the polymers coupled with the ability to tune their hydrophobicity and the high acid sensitivity of the microparticles identify this new class of materials as promising candidates for the delivery of bioactive materials.
Self-organizing maps (SOMs) are a relative newcomer to synoptic climatology; the method itself has only been utilized in the field for around a decade. In this article, we review the major developments and climatological applications of SOMs in the literature. The SOM can be used in synoptic climatological analysis in a manner similar to most other clustering methods. However, as the results from a SOM are generally represented by a two-dimensional array of cluster types that 'self-organize', the synoptic categories in the array effectively represent a continuum of synoptic categorizations, compared with discrete realizations produced through most traditional methods. Thus, a larger number of patterns can be more readily understood, and patterns, as well as transitional nodes between patterns, can be discerned. Perhaps the most intriguing development with SOMs has been the new avenues of visualization; the resultant spatial patterns of any variable can be more readily understood when displayed in a SOM. This improved visualization has led to SOMs becoming an increasingly popular tool in various research with climatological applications from other disciplines as well.
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