Core-shell microspheres with surface grafted poly(vinyl alcohol) as drug carriers for the treatment of hepatocellular carcinoma

Core(polyvinyl neodecanoate-ethylene glycol dimethacrylate)-shell(polyvinyl alcohol) (core (P(VND-EGDMA))-shell(PVA)) microspheres were developed by seeded polymerization with the use of conventional free radical and RAFT/MADIX mediated polymerization. Poly(vinyl pivalate) PVPi was grafted onto microspheres prepared via suspension polymerization of vinylneodecanoate and ethylene glycol dimethacrylate. The amount of grafted polymer was found to be independent from the technique used with conventional free radical polymerization and MADIX polymerization resulting into similar shell thicknesses. Both systems—grafting via free radical polymerization or the MADIX process—were found to follow slightly different kinetics. While the free radical polymerization resulted in a weight gain linear with the monomer consumption in solution the growth in the MADIX controlled system experienced a delay. The core-shell microspheres were obtained by hydrolysis of the poly(vinyl pivalate) surface grafted brushes to form poly(vinyl alcohol). During hydrolysis the microspheres lost a significant amount of weight, consistent with the hydrolysis of 40–70% of all VPi units. Drug loading was found to be independent of the shell layer thickness, suggesting that the drug loading is governed by the amount of bulk material. The shell layer does not appear to represent an obstacle to the drug ingress. Cell testing using colorectal cancer cell lines HT 29 confirm the biocompatibility of the empty microspheres whereas the clofazimine loaded particles lead to 50% cell death, confirming the release of the drug.

Non-invasive, quantitative analysis of drug mixtures in containers using spatially offset Raman spectroscopy (SORS) and multivariate statistical analysis

In this paper, spatially offset Raman spectroscopy (SORS) is demonstrated for non-invasively investigating the composition of drug mixtures inside an opaque plastic container. The mixtures consisted of three components including a target drug (acetaminophen or phenylephrine hydrochloride) and two diluents (glucose and caffeine). The target drug concentrations ranged from 5% to 100%. After conducting SORS analysis to ascertain the Raman spectra of the concealed mixtures, principal component analysis (PCA) was performed on the SORS spectra to reveal trends within the data. Partial least squares (PLS) regression was used to construct models that predicted the concentration of each target drug, in the presence of the other two diluents. The PLS models were able to predict the concentration of acetaminophen in the validation samples with a root-mean-square error of prediction (RMSEP) of 3.8% and the concentration of phenylephrine hydrochloride with an RMSEP of 4.6%. This work demonstrates the potential of SORS, used in conjunction with multivariate statistical techniques, to perform non-invasive, quantitative analysis on mixtures inside opaque containers. This has applications for pharmaceutical analysis, such as monitoring the degradation of pharmaceutical products on the shelf, in forensic investigations of counterfeit drugs, and for the analysis of illicit drug mixtures which may contain multiple components.

Assessment of function and clinical utility of alcohol and other drug web sites : an observational, qualitative study

Background The increasing popularity and use of the internet makes it an attractive option for providing health information and treatment, including alcohol/other drug use. There is limited research examining how people identify and access information about alcohol or other drug (AOD) use online, or how they assess the usefulness of the information presented. This study examined the strategies that individuals used to identify and navigate a range of AOD websites, along with the attitudes concerning presentation and content. Methods Members of the general community in Brisbane and Roma (Queensland, Australia) were invited to participate in a 30-minute search of the internet for sites related to AOD use, followed by a focus group discussion. Fifty one subjects participated in the study across nine focus groups. Results Participants spent a maximum of 6.5 minutes on any one website, and less if the user was under 25 years of age. Time spent was as little as 2 minutes if the website was not the first accessed. Participants recommended that AOD-related websites should have an engaging home or index page, which quickly and accurately portrayed the site’s objectives, and provided clear site navigation options. Website content should clearly match the title and description of the site that is used by internet search engines. Participants supported the development of a portal for AOD websites, suggesting that it would greatly facilitate access and navigation. Treatment programs delivered online were initially viewed with caution. This appeared to be due to limited understanding of what constituted online treatment, including its potential efficacy. Conclusions A range of recommendations arise from this study regarding the design and development of websites, particularly those related to AOD use. These include prudent use of text and information on any one webpage, the use of graphics and colours, and clear, uncluttered navigation options. Implications for future website development are discussed.

Screening for alcohol and drug use in pregnancy

Objective - this study examined the clinical utility and precision of routine screening for alcohol and other drug use among women attending a public antenatal service. Study design - a survey of clients and audit of clinical charts. Participants and setting - clients attending an antenatal clinic of a large tertiary hospital in Queensland, Australia, from October to December 2009. Measurements and findings - data were collected from two sources. First, 32 women who reported use of alcohol or other drugs during pregnancy at initial screening were then asked to complete a full substance use survey. Second, data were collected from charts of 349 new clients who attended the antenatal clinic during the study period. Both sensitivity (86%, 67%) and positive predictive value (100%, 92%) for alcohol and other drug use respectively, were high. Only 15% of surveyed women were uncomfortable about being screened for substance use in pregnancy, yet the chart audit revealed poor staff compliance. During the study period, 25% of clients were either not screened adequately or not at all. Key conclusions and implications for practise - despite recommended universal screening in pregnancy and the apparent acceptance by our participants, alcohol and other drug (A&OD) screening in the antenatal setting remains problematic. Investigation into the reasons behind, and ways to overcome, the low screening rate could improve health outcomes for mothers and children in this at-risk group. Targeted education and training for midwives may form part of the solution as these clinicians have a key role in implementing prevention and early intervention strategies.

Youth alcohol and drug good practice guide 1 : a framework for youth alcohol and other drug practice

This Guide outlines a framework for working with young people whose AOD use creates significant vulnerability to current or future harm. The target audience is practitioners who work with young people who have problematic AOD use and the managers of these practitioners. Areas of content include the elements of a framework for AOD practice, an appreciation of the developmental, social and institutional location of young people, key concepts and understandings regarding good youth centered context responsive practice, and key policy constructs and directions.

The role of education and awareness in workplace alcohol and drug use in the Australian construction industry : proposed program of research and preliminary results

The main aim of this paper is to outline a proposed program of research which will attempt to quantify the extent of the problem of alcohol and other drugs in the Australian construction industry, and furthermore, develop an appropriate industry-wide policy and cultural change management program and implementation plan to address the problem. This paper will also present preliminary results from the study. The study will use qualitative and quantitative methods (in the form of interviews and surveys, respectively) to evaluate the extent of the problem of alcohol and other drug use in this industry, to ascertain the feasibility of an industry-wide policy and cultural change management program, and to develop an appropriate implementation plan. The study will be undertaken in several construction organisations, at selected sites in South Australia, Victoria and Northern Territory. It is anticipated that approximately 500 employees from the participating organisations across Australia will take part in the study. The World Health Organisation’s Alcohol Use Disorders Identification Test (AUDIT) will be used to measure the extent of alcohol use in the industry. Illicit drug use, ‘‘readiness to change’’, impediments to reducing impairment, feasibility of proposed interventions, and employee attitudes and knowledge regarding workplace AOD impairment, will also be measured through a combination of interviews and surveys. Among the preliminary findings, for 51% (n=127) of respondents, score on the AUDIT indicated alcohol use at hazardous levels. Of the respondents who were using alcohol at hazardous levels, 76% reported (n97) that they do not have a problem with drinking and 54% (n=68) reported that it would be easy to ‘‘cut down’’ or stop drinking. Nearly half (49%) of all respondents (n=122) had used marijuana/cannabis at some time prior to being surveyed. The use of other illicit substances was much less frequently reported. Preliminary interview findings indicated a lack of adequate employee knowledge regarding the physical effects of alcohol and other drugs in the workplace. As for conclusions, the proposed study will address a major gap in the literature with regard to the extent of the problem of alcohol and other drug use in the construction industry in Australia. The study will also develop and implement a national, evidence-based workplace policy, with the aim of mitigating the deleterious effects of alcohol and other drugs in this industry.

The duplicitous nature of inflammation in wound repair

Skin plays a key role in protecting the body from the onslaught of pathogens and toxins we meet during our lifetime; thus, out of necessity, we have developed a rapid repair mechanism that quickly plugs any holes in this vital organ. Upon injury, a series of highly coordinated overlapping events, that include inflammatory, proliferation and maturation phases, result in the hasty closure of the wound and restoration of skin integrity. Over the past decade it has become clear that a number of immune cells that regulate the inflammatory phase, whilst important for removal of invading pathogens, are not necessary for repair and in fact may be responsible for the subsequent scar formation that seems to have resulted from having such a rapid repair process. The magnitude and length of inflammation in the wound not only appears to dictate the extent of scar formation but also in some cases may even prevent wound closure. In this review we will explore the two sides of inflammation in wound healing and review current and future drug therapies that target inflammation to modulate the healing outcome.

The FAM deubiquitylating enzyme localizes to multiple points of protein trafficking in epithelia, where it associates with E-cadherin and β-catenin

Ubiquitylation is a necessary step in the endocytosis and lysosomal trafficking of many plasma membrane proteins and can also influence protein trafficking in the biosynthetic pathway. Although a molecular understanding of ubiquitylation in these processes is beginning to emerge, very little is known about the role deubiquitylation may play. Fat Facets in mouse (FAM) is substrate-specific deubiquitylating enzyme highly expressed in epithelia where it interacts with its substrate, β-catenin. Here we show, in the polarized intestinal epithelial cell line T84, FAM localized to multiple points of protein trafficking. FAM interacted with β-catenin and E-cadherin in T84 cells but only in subconfluent cultures. FAM extensively colocalized with β-catenin in cytoplasmic puncta but not at sites of cell-cell contact as well as immunoprecipitating with β-catenin and E-cadherin from a higher molecular weight complex (~500 kDa). At confluence FAM neither colocalized with, nor immunoprecipitated, β-catenin or E-cadherin, which were predominantly in a larger molecular weight complex (~2 MDa) at the cell surface. Overexpression of FAM in MCF-7 epithelial cells resulted in increased β-catenin levels, which localized to the plasma membrane. Expression of E-cadherin in L-cell fibroblasts resulted in the relocalization of FAM from the Golgi to cytoplasmic puncta. These data strongly suggest that FAM associates with E-cadherin and β-catenin during trafficking to the plasma membrane.

Youth alcohol and drug practice guide 2: Legal and ethical dimensions of practice

This Guide is designed to assist workers better understand the and negotiate the complex interplay of ethical, legal and organisational considerations in their practice. The goal is to provide frontline workers and managers with information, questions and principles which promote good youth AOD practice. Legal information provided relates to Queensland, Australia.