Mesoporous bioactive glasses as drug delivery and bone tissue regeneration platforms

The use of mesoporous bioactive glasses (MBG) for drug delivery and bone tissue regeneration has grown significantly over the past 5 years. In this review, we highlight the recent advances made in the preparation of MBG particles, spheres, fibers and scaffolds. The advantages of MBG for drug delivery and bone scaffold applications are related to this material’s well-ordered mesopore channel structure, superior bioactivity, and the application for the delivery of both hydrophilic and hydrophobic drugs. A brief forward-looking perspective on the potential clinical applications of MBG in regenerative medicine is also discussed.

Neuronal nicotinic acetylcholine receptors as pharmacotherapeutic targets for the treatment of alcohol use disorders

Alcohol use disorders (AUDs) are complex and developing effective treatments will require the combination of novel medications and cognitive behavioral therapy approaches. Epidemiological studies have shown there is a high correlation between alcohol consumption and tobacco use, and the prevalence of smoking in alcoholics is as high as 80% compared to about 30% for the general population. Both preclinical and clinical data provide evidence that nicotine administration increases alcohol intake and nonspecific nicotinic receptor antagonists reduce alcohol-mediated behaviors. As nicotine interacts specifically with the neuronal nicotinic acetylcholine receptor (nAChR) system, this suggests that nAChRs play an important role in the behavioral effects of alcohol. In this review, we discuss the importance of nAChRs for the treatment of AUDs and argue that the use of FDA approved nAChR ligands, such as varenicline and mecamylamine, approved as smoking cessation aids may prove to be valuable treatments for AUDs. We also address the importance of combining effective medications with behavioral therapy for the treatment of alcohol dependent individuals.

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.

Acceptability of cognitive-behaviour therapy via the Internet for cessation of benzodiazepine use

Introduction and Aims: Long-term use of benzodiazepines remains common, and conveys significant risk. Providing psychological intervention in association with gradual dose reduction increases cessation rates above dose reduction alone, but appropriate psychological support is difficult to obtain. This study was undertaken to assess the outcomes of an uncontrolled case series of an internet-based cognitive-behaviour therapy (I-CBT) for benzodiazepine cessation. Design and Method: Users of benzodiazepines for > 3 months who wanted to reduce or cease benzodiazepines participated in the trial. They completed online assessments and accessed 13 newsletters on managing withdrawal symptoms and developing alternate ways to cope with life events. Therapist assistance was provided by email. Follow-up was at 3 and 6 months and feedback was obtained via comments and emails. Results: Program ratings and emailed comments of the program were positive. Thirty-two people registered for the program and 14 (44%) completed a 6-month follow-up. Of these, 8 (57%) reduced weekly intake by at least half, including 5 (36%) who ceased use. Shorter duration of use and birth outside Australia predicted greater percentage reductions at 3 months, while being partnered and in paid employment predicted reductions at 6 months. Discussion and Conclusion: While results were encouraging, controlled research is required to confirm the efficacy of the program, and engagement of both users and prescribers needs further attention.

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.

Studies on the surface properties of biodegradable polymer carriers in respiratory delivery of drug from Dry Powder Inhaler formulations

Dry Powder Inhaler (DPI) technology has a significant impact in the treatment of various respiratory disorders. DPI formulations consist of a micronized drug (<5ìm) blended with an inert coarse carrier, for which lactose is widely used to date. DPIs are one of the inhalation devices which are used to target the delivery of drugs to the lungs. Drug delivery via DPI formulations is influenced by the physico-chemical characteristics of lactose particles such as size, shape, surface roughness and adhesional forces. Commercially available DPI formulations, which utilise lactose as the carrier, are not efficient in delivering drug to the lungs. The reasons for this are the surface morphology, adhesional properties and surface roughness of lactose. Despite several attempts to modify lactose, the maximum efficient drug delivery to the lungs remains limited; hence, exploring suitable alternative carriers for DPIs is of paramount importance. Therefore, the objective of the project was to study the performance of spherical polymer microparticles as drug carriers and the factors controlling their performance. This study aimed to use biodegradable polymer microspheres as alternative carriers to lactose in DPIs for achieving efficient drug delivery into the lungs. This project focused on fabricating biodegradable polymer microparticles with reproducible surface morphology and particle shape. The surface characteristics of polymeric carriers and the adhesional forces between the drug and carrier particles were investigated in order to gain a better understanding of their influence on drug dispersion. For this purpose, two biodegradable polymers- polycaprolactone (PCL) and poly (DL-lactide-co-glycolide) (PLGA) were used as the carriers to deliver the anti-asthmatic drug - Salbutamol Sulphate (SS). The first study conducted for this dissertation was the aerosolization of SS from mixtures of SS and PCL or PLGA microparticles. The microparticles were fabricated using an emulsion technique and were characterized by laser diffraction for particle size analysis, Scanning Electron Microscopy (SEM) for surface morphology and X-ray Photoelectron Spectroscopy (XPS) to obtain surface elemental composition. The dispersion of the drug from the DPI formulations was determined by using a Twin Stage Impinger (TSI). The Fine particle Fraction (FPF) of SS from powder mixtures was analyzed by High Performance Liquid Chromatography (HPLC). It was found that the drug did not detach from the surface of PCL microspheres. To overcome this, the microspheres were coated with anti-adherent agents such as magnesium stearate and leucine to improve the dispersion of the drug from the carrier surfaces. It was found that coating the PCL microspheres helped in significantly improving the FPF of SS from the PCL surface. These results were in contrast to the PLGA microspheres which readily allowed detachment of the SS from their surface. However, coating PLGA microspheres with antiadherent agents did not further improve the detachment of the drug from the surface. Thus, the first part of the study demonstrated that the surface-coated PCL microspheres and PLGA microspheres can be potential alternatives to lactose as carriers in DPI formulations; however, there was no significant improvement in the FPF of the drug. The second part of the research studied the influence of the size of the microspheres on the FPF of the drug. For this purpose, four different sizes (25 ìm, 48 ìm, 100 ìm and 150 ìm) of the PCL and PLGA microspheres were fabricated and characterized. The dispersion of the drug from microspheres of different sizes was determined. It was found that as the size of the carrier increased there was a significant increase in the FPF of SS. This study suggested that the size of the carrier plays an important role in the dispersion of the drug from the carrier surface. Subsequent experiments in the third part of the dissertation studied the surface properties of the polymeric carrier. The adhesion forces existing between the drug particle and the polymer surfaces, and the surface roughness of the carriers were quantified using Atomic Force Microscopy (AFM). A direct correlation between adhesion forces and dispersion of the drug from the carrier surface was observed suggesting that adhesion forces play an important role in determining the detachment potential of the drug from the carrier surface. However, no direct relationship between the surface roughness of the PCL or PLGA carrier and the FPF of the drug was observed. In conclusion, the body of work presented in this dissertation demonstrated the potential of coated PCL microspheres and PLGA microspheres to be used in DPI formulations as an alternative carrier to sugar based carriers. The study also emphasized the role of the size of the carrier particles and the forces of interaction prevailing between the drug and the carrier particle surface on the aerosolization performances of the drug.

The effect of alcohol and drug consumption on academic performance : a treatment effect evaluation

It is often argued that consumption of alcohol, tobacco and drugs is detrimental to the cognitive abilities of teenagers. In order to disentangle a possible causal effect of these substances use from a self-selection bias, we control for pupils previous performance and for their previous rate of progression applying a DiDiD strategy. Using the NELS 1988 panel dataset, we find that the effects of alcohol and tobacco on test scores disappear once the selection bias is controlled for (this does not preclude long term detrimental effects). However, we find reliable evidence that heavy use of drugs (marijuana and cocaine) has direct detrimental effects on educational achievements. Hence, our results may have significant policy implications.

Screening and managing cannabis use: comparing GP's and nurses' knowledge, beliefs, and behavior

Background: General practitioners (GPs) and nurses are ideally placed to address the significant unmet demand for the treatment of cannabis-related problems given the numbers of people who regularly seek their care. The aim of this study was to evaluate differences between GPs and nurses’ perceived knowledge, beliefs, and behaviors toward cannabis use and its screening and management. Methods: This study involved 161 nurses and 503 GPs who completed a survey distributed via conference satchels to delegates of Healthed seminars focused on topics relevant to women and children’s health. Differences between GPs and nurses were analyzed using χ2- tests and two-sample t-tests, while logistic regression examined predictors of service provision. Results: GPs were more likely than nurses to have engaged in cannabis-related service provision, but also more frequently reported barriers related to time, interest, and having more important issues to address. Nurses reported less knowledge, skills, and role legitimacy. Perceived screening skills predicted screening and referral to alcohol and other drug (AOD) services, while knowing a regular user increased the likelihood of referrals only. Conclusions: Approaches to increase cannabis-related screening and intervention may be improved by involving nurses, and by leveraging the relationship between nurses and doctors, in primary care.

Synthesis of an erodible biomimetic hydrogel for drug delivery using native chemical ligation

Hydrogels are hydrophilic, three dimensional polymers that imbibe large quantities of water while remaining insoluble in aqueous solutions due to chemical or physical cross-linking. The polymers swell in water or biological fluids, immobilizing the bioactive agent, leading to drug release in a well-defined specific manner. Thus the hydrogels’ elastic properties, swellability and biocompatibility make them excellent formulations for drug delivery. Currently, many drug potencies and therapeutic effects are limited or otherwise reduced because of the partial degradation that occurs before the administered drug reaches the desired site of action. On the other hand, sustained release medications release drugs continually, rather than providing relief of symptoms and protection solely when necessary. In fact, it would be much better if drugs could be administered in a manner that precisely matches physiological needs at desired times and at the desired site (site specific targeting). There is therefore an unmet need to develop controlled drug delivery systems especially for delivery of peptide and protein bound drugs. The purpose of this project is to produce hydrogels for structural drug delivery and time-dependent sustained release of drugs (bioactive agents). We use an innovative polymerisation strategy based on native chemical ligation (NCL) to covalently cross-link polymers to form hydrogels. When mixed in aqueous solution, four armed (polyethylene glycol) amine (PEG-4A) end functionalised with thioester and four branched Nterminal cysteine peptide dendrimers spontaneously conjugated to produce biomimetic hydrogels. These hydrogels showed superior resistance to shear stress compared to an equivalent PEG macromonomer system and were shown to be proteolytically degradable with concomitant release of a model payload molecule. This is the first report of a peptide dendrimers/PEG macromonomer approach to hydrogel production and opens up the prospect of facile hydrogel synthesis together with tailored payload release.

Youth Alcohol and Drug Practice Guide 3 : Practice Strategies and Interventions

This guide canvasses a range of practice strategies and interventions utilised by workers and services who engage with young people experiencing problematic AOD use whilst also exploring the many and varied challenges associated with this type of work.

Patients with terminal cancer who use alternative therapies: their beliefs and practices

This paper examines the extent to which patients who have been diagnosed as having terminal cancer choose to use non-medical therapies. In particular it is concerned with the illness behaviour of patients who are receiving conventional cytotoxic drug and radiation treatments, who also decide to use a wide range of ‘alternative’ medications and therapies. The paper discusses the findings of a study of 152 patients with metastatic cancer that examined the extent to which they used alternative cancer therapies, as well as the beliefs and attitudes they have about their cancer, its treatment, and the practitioners providing that treatment. Four groups of users of alternative therapies, who differ according to their commitment to and the type of therapies they use, were identified. Results of logistic regression analyses indicate that those using alternative therapies were different in range of social attitudes. These differences were primarily their greater reported ‘will to live’ and desire for control over treatment decisions, and the differing beliefs they hold about their disease.

Results of the Queensland 2007-2012 roadside drug testing program : the prevalence of three illicit drugs

The purpose of this investigation is to present an overview of roadside drug driving enforcement and detections in Queensland, Australia since the introduction of oral fluid screening. Drug driving is a problematic issue for road safety and investigations of the prevalence and impact of drug driving suggest that, in particular, the use of illicit drugs may increase a driver’s involvement in a road crash when compared to a driver who is drug free. In response to the potential increased crash involvement of drug impaired drivers, Australian police agencies have adopted the use of oral fluid analysis to detect the presence of illicit drugs in drivers. This paper describes the results of roadside drug testing for over 80,000 drivers in Queensland, Australia, from December 2007 to June 2012. It provides unique data on the prevalence of methamphetamine, cannabis and ecstasy in the screened population for the period. When prevalence rates are examined over time, drug driving detection rates have almost doubled from around 2.0% at the introduction of roadside testing operations to just under 4.0% in the latter years. The most common drug type detected was methamphetamine (40.8%) followed by cannabis (29.8%) and methamphetamine/cannabis combination (22.5%). By comparison, the rate of ecstasy detection was very low (1.7%). The data revealed a number of regional, age and gender patterns and variations of drug driving across the state. Younger drivers were more likely to test positive for cannabis whilst older drivers were more likely to test positive for methamphetamine. The overall characteristics of drivers who tested positive to the presence of at least one of the target illicit drugs are they are likely to be male, aged 30-39 years, be driving a car on Friday, Saturday or Sunday between 6:00PM and 6:00AM and to test positive for methamphetamine.

Psychotropic medication use in adolescents with intellectual disability living in the community

Purpose Information on the use of psychotropic medications in adolescents with intellectual disability is scant. Such information can guide interventions to improve psychotropic medication use in this population. We investigated the prevalence of, and factors associated with, psychotropic medication use in adolescents with intellectual disability in Australia who live in the community. Methods Cross-sectional data were obtained from adolescents with intellectual disability living in the community in South East Queensland, Australia, between February 2007 and September 2010. Self-reported information on medication use was extracted from a health screening tool. Demographic and medical data were collected through parent/caregiver surveys. Medications were classified according to the Anatomical Therapeutic Chemical classification system. Psychopathology was assessed using the Developmental Behaviour Checklist Short Form. Logistic regression analysis was used to assess the association of demographic and medical characteristics with psychotropic medication use. Results There were 176 participants (median age = 16 years, range = 11–19 years; 55% male). Psychotropics were used by 20% of participants. Psychostimulants were the commonest psychotropic class, used by 9% of participants. Multipsychotropic prescribing was not common with only seven participants using more than one psychotropic agent. After adjusting for potentially confounding variables, use of psychotropic medications was significantly associated with male gender (adjusted odds ratio = 3.6; 95% confidence interval = 1.3–9.5) and having major behaviour problems (3.1; 1.1–8.9). Conclusions Adolescents with intellectual disability use a wide range of psychotropic medications. Being male and having major behaviour problems are associated with the use of psychotropic medications. Research examining the rationale for psychotropic prescribing in this population is needed. Copyright © 2013 John Wiley & Sons, Ltd.