Hyaluronic acid (HA) hydrogels are attractive materials for biomedical applications because they are porous, water-swelling, biocompatible, biodegradable, and resistant to non-specific cell adhesion. A limitation of HA hydrogels is that incorporation of bioactive drugs can be restricted by low solubility of drug within the hydrogel environment. Our goal was to synthesize HA hydrogels that bind drug through hydrophobic interactions as a method for increasing drug loading. We functionalized photocrosslinked HA hydrogels with a methacryloyl derivative of beta-cyclodextrin (betaCD). betaCD is a molecular "basket" with a hydrophilic exterior and a hydrophobic cavity. Inclusion complexes are formed when betaCD hosts all or part of a hydrophobic drug within the cavity. HA hydrogels functionalized with methacryloyl-betaCD monomer gained the property of inclusion complexation which greatly enhanced the uptake of a model hydrophobic drug, hydrocortisone. Pre-incubation of the hydrogels with adamantane carboxylic acid (ACA) inhibited hydrocortisone uptake by competition for betaCD cavities. In addition, control hydrogels of HA functionalized with alphaCD monomer were not efficient at hydrocortisone uptake because the alphaCD cavity is too small for efficient complexation. These experiments confirmed that the betaCD monomer enhances drug loading by the mechanism of inclusion complexation. Drug-binding HA-betaCD hydrogels may be further engineered to create HA-based biomaterials with a built in drug delivery capability.
Improving our understanding of these issues is an essential first step to protect human participants in future EMA research. We provide a brief set of recommendations that can aid in the design and ethics review of the future EMA protocol with substance using populations.
Background: While studies have documented both the feasibility and acceptability of using ecological momentary assessment (EMA) to study drug use, there is little empirical research assessing participants' perceptions of utilizing this technology-driven approach.Methods: Participants were English-speaking persons ≥18 years old who reported injection drug use and sequential (e.g., alcohol followed by opioid use) or simultaneous (i.e., injecting heroin and cocaine in one shot) polydrug use within 30 days recruited in San Diego, CA and Philadelphia, PA. Participants (N=36) completed two cell phone-based EMA simulations assessing mood, drug use, HIV risk behaviors, and daily activities, followed by semi-structured interviews that probed for potential benefits of participation over time.Qualitative analysis involved an iterative process of reviewing texts from the interviews to create a coding framework, which was then applied to all transcripts to identify themes.Results: Findings suggest participants may derive indirect benefits from participation in EMA studies including: improved self-worth from helping others; experiencing increased social support through utilization of the study-provided mobile device for non-research purposes; and most importantly, increased self-reflection, which could lead to therapeutic and intervention-like effects such as decreased substance use or reduced HIV risk. Conclusions:Participants identified a variety of potential benefits from participating in a study that utilizes EMA. This research suggests that benefits are highly salient for individuals involved in studies of polydrug use.
OBJECTIVE -To compare direct-measured HDL cholesterol with HDL cholesterol measured by a precipitation method. RESEARCH DESIGN AND METHODS-We compared a homogeneous assay for direct HDL cholesterol analysis with the phosphotungstic acid magnesium chloride precipitation method in 55 type 1 diabetic patients, 70 type 2 diabetic patients, and 82 nondiabetic normal control subjects with plasma triglyceride levels Ͻ4.6 mmol/l. The cholesterol content of HDL determined by the direct assay was overall 0.1 mmol/l higher in all three groups than HDL cholesterol measured after precipitation, but the two methods were closely correlated (r 2 ϭ 0.98, P Ͻ 0.001).RESULTS -HbA 1c , blood glucose, serum albumin, serum bilirubin, or triglyceride did not influence the differences of the two HDL cholesterol measurements. Because we have previously shown HDL cholesterol isolated by phosphotungstic acid precipitation to be lower than that by ultracentrifugation, the positive bias found in this study was expected. It seems that the direct HDL cholesterol assay reacts with apolipoprotein (apo) B-containing lipoproteins in the fraction with a density of Ͼ1.063; these apo B-containing lipoproteins are suggested to be coprecipitated with the phosphotungstic acid method. We also measured LDL cholesterol directly by a LDL cholesterol plus method and found no significant differences between this method and LDL cholesterol calculated from Friedewald's formula.CONCLUSIONS -Direct homogeneous assay for HDL cholesterol determination in diabetic patients seems not to exhibit a negative bias, in contrast to the precipitation method, when compared with the ultracentrifugation method. In addition, the direct assay saves time and is not influenced by type of diabetes or degree of metabolic control.
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