Most therapeutic agents suffer from poor solubility, rapid clearance from the blood stream, a lack of targeting, and often poor translocation ability across cell membranes. Drug/gene delivery systems ...(DDSs) are capable of overcoming some of these barriers to enhance delivery of drugs to their right place of action, e.g. inside cancer cells. In this review, we focus on nanoparticles as DDSs. Complementary experimental and computational studies have enhanced our understanding of the mechanism of action of nanocarriers and their underlying interactions with drugs, biomembranes and other biological molecules. We review key biophysical aspects of DDSs and discuss how computer modeling can assist in rational design of DDSs with improved and optimized properties. We summarize commonly used experimental techniques for the study of DDSs. Then we review computational studies for several major categories of nanocarriers, including dendrimers and dendrons, polymer-, peptide-, nucleic acid-, lipid-, and carbon-based DDSs, and gold nanoparticles. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov.
Display omitted
•Nanoparticles have the potential to improve drug delivery and enable precision medicine.•Nanoparticles for drug delivery can be based on many different chemistries.•We review experimental and computational approaches to study nanoparticles for drug delivery.
The α-oxocarboxylates (α-ketocarboxylates) and the corresponding α-oxoacids (α-ketoacids) have been reported as byproducts of ozonation of potable water supplies. Some of these species also occur in ...biophysiological systems. Five analytes were investigated in this study: oxoethanoate (glyoxylate), 2-oxopropanoate (pyruvate), 2-oxobutanoate (2-ketobutyrate), 2-oxopentanoate (2-ketovalerate) and oxopropanedioate (ketomalonate, mesoxalate). Ion chromatography (IC) and gas chromatography (GC) were evaluated for the quantitation of these analytes at concentrations ≤200 ng ml
−1. For the IC method, the samples are run directly with minimal to no pre-treatment. For the GC method, the analytes must be derivatized with
O-(2,3,4,5,6-pentafluorobenzyl)oxylamine to form oximes. The oximes are extracted into
tert.-butyl methyl ether and the carboxylic acid is esterified (methylated) with diazomethane. It was concluded that the ion chromatographic determination is significantly superior to the gas chromatographic method for these analytes.
The American Stroke Association (ASA) assembled a multidisciplinary group of experts to develop recommendations regarding the potential effectiveness of establishing an identification program for ...stroke centers and systems. "Identification" refers to the full spectrum of models for assessing and recognizing standards of quality care (self-assessment, verification, certification, and accreditation). A primary consideration is whether stroke center identification might improve patient outcomes.
In February 2001, ASA, with the support of the Stroke Council's Executive Committee, decided to embark on an evaluation of the potential impact of stroke center identification. HealthPolicy R&D was selected to prepare a comprehensive report. The investigators reported on models outside the area of stroke, ongoing initiatives within the stroke community (such as Operation Stroke), and state and federal activities designed to improve care for stroke patients. The investigators also conducted interviews with thought leaders in the stroke community, representing a diverse sampling of specialties and affiliations. In October 2001, the Advisory Working Group on Stroke Center Identification developed its consensus recommendations. This group included recognized experts in neurology, emergency medicine, emergency medical services, neurological surgery, neurointensive care, vascular disease, and stroke program planning.
There are a variety of existing identification programs, generally falling within 1 of 4 categories (self-assessment, verification, certification, and accreditation) along a continuum with respect to intensity and scope of review and consumption of resources. Ten programs were evaluated, including Peer Review Organizations, trauma centers, and new efforts by the National Committee on Quality Assurance and the Joint Commission on the Accreditation of Healthcare Organizations to identify providers and disease management programs. The largest body of literature on clinical outcomes associated with identification programs involves trauma centers. Most studies support that trauma centers and systems lead to improved mortality rates and patient outcomes. The Advisory Working Group felt that comparison to the trauma model was most relevant given the need for urgent evaluation and treatment of stroke. The literature in other areas generally supports the positive impact of identification programs, although patient outcomes data have less often been published. In the leadership interviews, participants generally expressed strong support for pursuing some form of voluntary identification program, although concerns were raised that this effort could meet with some resistance.
Identification of stroke centers and stroke systems competencies is in the best interest of stroke patients in the United States, and ASA should support the development and implementation of such processes. The purpose of a stroke center/systems identification program is to increase the capacity for all hospitals to treat stroke patients according to standards of care, recognizing that levels of involvement will vary according to the resources of hospitals and systems.
The role of myocardial infarction was investigated in 121 cases of sudden death with atherosclerotic heart disease. In addition to supporting other reports which have demonstrated the importance of ...chronic occlusion of the coronary vessels in relation to the high rate of infarctions found in such cases, the authors presented evidence which showed differences in occurrence in the sites of remote and recent infarctions, a lack of concordance between the sites of recent infarctions, and acute thrombosis in coronary vessels proximal to these lesions. No relationship between patient age or prior symptoms could be associated with the occurrence of infarction. Evidence was also presented which discounted the possible role of transmural infarction in the formation of acute thrombosis. These pathological observations support the concept that sudden cardiac deaths are results of functional instability of the myocardium produced by advanced coronary atherosclerosis.
The significance of organizing thrombosis was investigated in 121 cases of sudden death with atherosclerotic heart disease. Organizing thrombosis was observed in one-third of the cases, and sites at ...which it was present showed a higher prevalence of acute lesions -- thrombus, plaque rupture, and hemorrhage -- than sites at which it was not present. Acute and subacute coronary lesions were almost entirely restricted to vessels with 75% or greater obstruction. Evidence was presented suggesting that the organization of thrombosis in the coronary arteries was a more extended process than that observed in peripheral arteries.
PDF
