A Qualitative Evaluation of the Australian Community Pharmacy Agreement.

The Australian Federal Government's Community Pharmacy Agreement (Agreement), initiated in 1990 and renegotiated every five years with a pharmacy owners' organisation, is the dominant policy directing community pharmacy. We studied the experience with the Agreements of 38 purposively selected individual pharmacists and others of diverse backgrounds, using in-depth, semi-structured interviews. Although perceived to lack transparency in negotiation and operation, as well as paucity of outcome measures, the Agreements have generally supported the viability of community pharmacies and on balance, contributed positively to the public's access to medicines. There were, however, contradictory opinions regarding the impact of the policy's regulation of pharmacy locations, including the suggestion that they provide existing owners with an undue commercial advantage. A reported shortcoming of the Agreements was their impact on pharmacists' abilities to expand their scopes of practice and assist patients to make better use of medicines, in part due to the funding being almost totally focused on supply-related functions. The support for programs such as medication management services was perceived to be limited, and opportunities for diversification in pharmacy practice appeared constrained. Future pharmacy policy developed by the government could be more inclusive of a diverse range of stakeholders, seek to better utilise pharmacists' expertise, and have a greater focus on health outcomes.

An evaluation of the Australian Community Pharmacy Agreement from a public policy perspective: industry policy cloaked as health policy?

BACKGROUND: A series of Community Pharmacy Agreements (Agreements) between the Federal government and a pharmacy-owners' body, the Pharmacy Guild of Australia (PGA) have been influential policy in Australian community pharmacy (CP) since 1990. While ostensibly to support the public's access and use of medicines, the core elements of the Agreements have been remuneration for dispensing and rules that limit the establishment of new pharmacies. Criticism has focused on the self-interest of pharmacy owners, the exclusion of other pharmacy stakeholders from the Agreement negotiations, the lack of transparency, and the impact on competition. The objective of this paper is to determine the true nature of the policy by examining the evolution of the CPA from a policy theory perspective. METHODS: A qualitative evaluation of all seven Agreement documents and their impact was undertaken using policy theories including a linear policy development model, Multiple Streams Framework, Incremental Theory, the Advocacy Coalition Framework, the Theory of Economic Regulation, the Punctuated Equilibrium Framework, and Elite Theory. The Agreements were evaluated using four lenses: their objectives, evidentiary base, stakeholders and beneficiaries. RESULTS: The PGA has acted as an elite organisation with long-standing influence on the policy's development and implementation. Notable has been the failure of other pharmacy stakeholders to establish broad-based advocacy coalitions in order to influence the Agreements. The incremental changes negotiated every 5 years to the core elements of the Agreements have supported the publics' access to medication, provided stability for the government, and security for existing pharmacy owners. Their impact on the evolution of pharmacists' scope of practice and through that, on the public's safe and appropriate use of medication, has been less clear. CONCLUSIONS: The Agreements can be characterised predominantly as industry policy benefiting pharmacy owners, rather than health policy. An emerging issue is whether incremental change will continue to be an adequate policy response to the social, political, and technological changes that are affecting health care, or whether policy disruption is likely to arise.

Characterization of polymethylmethacrylate microspheres loaded with silver and doxycycline for dental materials applications.

OBJECTIVES: The manufacturing of polymethylmethacrylate(PMMA) microspheres loaded with doxycycline(DOX) and/or silver sulfate(Ag2SO4) to be incorporated into glass ionomer cement(GIC). METHODS: PMMA microspheres were manufactured with Ag2SO4(1-5%) and/or DOX(5-15%). Particle size, encapsulation efficiency and drug release were measured by light microscope, ICP, and HPLC. Microspheres were added to a dental GIC(20%w/w). Drug release and DTS were investigated. Minimum inhibitory concentration and antibacterial effects of PMMA microspheres into GIC materials were tested. RESULTS: The median diameter of 50 µm was obtained for microspheres. DOX was encapsulated at an efficiency of 8.3% using a theoretical loading of 15%DOX + 5%Ag2SO4. The Ag2SO4 encapsulation efficiency was 0.63% using a theoretical loading of 5%AgSO4. All groups showed burst release within the first day and continued released up to 15 days, with 60-83% of DOX and approximately 30% of silver. For GIC, approximately 15% of DOX and 0.18% of silver were released in a 7-day period. Microbiological results showed an antimicrobial effect against S. mutans when the lead formulation of microspheres was added. The DTS was reduced by the inclusion of microspheres. SIGNIFICANCE: PMMA microspheres containing DOX and Ag2SO4 offer a sustained antimicrobial activity for dental applications and promising potential for the biomedical field.

Controlled and localized antibiotics delivery using magnetic-responsive beads for synergistic treatment of orthopedic infection.

Antibiotic-loaded bone cement beads have been a reliable passive delivery system for the localized treatment of osteomyelitis; however, low, and unregulated drug release rates limit the ability of this system to maintain therapeutic concentrations. This problem is further amplified by drug-resistant pathogens that might invade or evolve under these conditions. Furthermore, currently available bone cements are incompatible with some antibiotics. The proposed device resembles conventional bone cement beads but contains an on-demand drug delivery magnetic sponge that provides actively controlled release of antibiotics. The slightly porous structure facilitates some drug diffusion while further drug release may be controlled remotely via magnetic actuation. Additionally, a combination of silver nitrate and gentamicin are used in the device as these agents are shown to display a synergistic antibacterial activity in vitro using checkerboard and time-kill assays. The device releases gentamicin and silver in both actuation and diffusion modes over 7 days. The in vitro bacterial studies demonstrate the efficacy of the released agents alone, and synergistically in combination, against Methicillin-resistant Staphylococcus aureus and Escherichia coli. The proposed device offers a facile fabrication process which allows control of the release profile by engineering hole configurations or manipulating magnetic field strength to provide the most effective therapy.

Analysis of the demographics and characteristics of the Australian pharmacist workforce 2013-2018: decreasing supply points to the need for a workforce strategy.

OBJECTIVES: An adequate workforce is necessary for health care delivery. The last official analysis of the Australian pharmacist workforce was in 2014 and the results of recent studies are contradictory. The objective of this work was to determine current demographic details and recent trends of the pharmacy workforce and assess the impact of changes in student numbers and migration policy. METHODS: Longitudinal and descriptive analysis was undertaken of National Health Workforce Datasets and registrant data available from the Australian Health Practitioner Regulation Agency and the Pharmacy Board of Australia from 2013 to 2018. KEY FINDINGS: There was an increase in females and a trend towards hospital practice but no change in the geographic distribution of pharmacists over the period. However, the pharmacist workforce grew more slowly than comparable health professions and while the youngest pharmacist cohort (20-34 years) remains the largest, the next oldest cohort increased at a greater rate. The youngest cohort reported a decrease in intention to remain working in pharmacy. CONCLUSIONS: A fall in student numbers and changes to immigration policy have contributed to a low growth rate and ageing of the pharmacist workforce compared with other professions. Whether these factors along with the intentions of young pharmacists will result in a shortage is dependent on developments in demand for pharmacists and a workforce strategy is required to monitor these developments.

A polymeric paste-drug formulation for local treatment of upper tract urothelial carcinoma.

BACKGROUND: Intravesical instillation of chemo- or immunotherapy is commonly used in bladder cancer. Upper tract urothelial carcinoma (UTUC) shares similar pathological features, but current formulations are not suitable for direct instillation to the upper urinary tract. OBJECTIVE: To evaluate in vivo applicability, characteristics and toxicity of ST-UC, a mucoadhesive polymeric paste formulation of gemcitabine, for upper urinary tract instillation. MATERIAL AND METHODS: Three pigs received 10 ml of ST-UC (100 mg/ml gemcitabine) retrogradely into 1 renal pelvis for pharmacokinetic studies. Four days later, a second injection into the contralateral renal pelvis was followed by serial euthanasia of the pigs and nephroureterectomy after 1, 3, and 6 hours. Adverse effects were monitored. Urine, serum, and tissue gemcitabine concentrations were measured, along with histologic examination of the upper urinary tract. RESULTS: Retrograde instillation of ST-UC was well tolerated with mild, completely receding hydronephrosis. Urine gemcitabine concentrations were highest in the first 3-hour collection interval. Hundred percent of gemcitabine was recovered in the urine within 24 hours. Serum peak concentrations (cmax) of gemcitabine were low at 5.5 µg/ml compared to the 10 to 30 µg/ml levels observed after a single intravenous dose of 1,000 mg/m2 gemcitabine. The formulation was still traceable after one hour and gemcitabine tissue concentrations are supportive of this extended drug exposure. No major histopathological changes were observed. The main limitation of this study is the lack of antitumor activity data. CONCLUSION: This preclinical evaluation of ST-UC demonstrated feasible instillation in the renal pelvis, no significant safety concerns, and sustained release of gemcitabine.

Oxygen limitation fails to explain upper chronic thermal limits and the temperature size rule in mayflies.

An inability to adequately meet tissue oxygen demands has been proposed as an important factor setting upper thermal limits in ectothermic invertebrates (especially aquatic species) as well as explaining the observed decline in adult size with increased rearing temperature during the immature stages (a phenomenon known as the temperature size rule, or TSR). We tested this by rearing three aquatic insects (the mayflies Neocloeon triangulifer and two species of the Cloeon dipterum complex) through their entire larval life under a range of temperature and oxygen concentrations. Hyperoxia did not extend upper thermal limits, nor did it prevent the loss of size or fertility experienced near upper chronic thermal limits. At moderate temperatures, the TSR pattern was observed under conditions of hyperoxia, normoxia and hypoxia, suggesting little or no influence of oxygen on this trend. However, for a given rearing temperature, adults were smaller and less fecund under hypoxia as a result of a lowering of growth rates. These mayflies greatly increased the size of their gills in response to lower dissolved oxygen concentrations but not under oxygen-saturated conditions over a temperature range yielding the classic TSR response. Using ommatidium diameter as a proxy for cell size, we found the classic TSR pattern observed under moderate temperature conditions was due primarily to a change in the number of cells rather than cell size. We conclude overall that a failure to meet tissue oxygen demands is not a viable hypothesis for explaining either the chronic thermal limit or TSR pattern in these species.

Transcriptomic and life history responses of the mayfly Neocloeon triangulifer to chronic diel thermal challenge.

To better understand the effects of transient thermal stress in an aquatic insect, we first identified static temperatures associated with fitness deficits, and then reared larvae from egg hatch to adulthood under diurnally variable regimens including daily forays into deleterious temperatures. We sampled mature larvae at the coolest and warmest portions of their respective regimens for RNA-seq analysis. Few transcripts (28) were differentially expressed when larvae oscillated between favorable temperatures, while 614 transcripts were differentially expressed when experiencing daily transient thermal stress. Transcripts associated with N-glycan processing were downregulated while those associated with lipid catabolism and chitin turnover were significantly upregulated in heat stressed larvae. An across-regimen comparison of differentially expressed transcripts among organisms sampled at comparable temperatures demonstrated that the effects of daily thermal stress persisted even when larvae were sampled at a more optimal temperature (806 differentially expressed transcripts). The chronically stressed population had reduced expression of transcripts related to ATP synthesis, mitochondrial electron chain functions, gluconeogenesis and glycolytic processes while transcripts associated with cell adhesion, synaptic vesicle transport, regulation of membrane potential and lipid biosynthesis increased. Comparisons of constant vs. variable temperatures revealed that the negative consequences of time spent at stressful temperatures were not offset by more time spent at optimal temperatures.

Strategies to promote access to medications during the COVID-19 pandemic.

BACKGROUND: During the COVID-19 pandemic, vulnerable and older people with chronic and complex conditions have self-isolated in their homes, potentially limiting opportunities for consultations to have medications prescribed and dispensed. OBJECTIVE: The aim of this article is to describe initiatives to ensure ongoing access to medications during the COVID-19 pandemic. DISCUSSION: Cooperation between wholesalers and purchase limits in pharmacies have helped to ensure supply of essential medications. Therapeutic substitution by pharmacists is permitted for specific products authorised by the Therapeutic Goods Administration. Prescribers are permitted to issue digital image prescriptions, and implementation of electronic prescribing has been fast-tracked. Expanded continued dispensing arrangements introduced during the bushfire crises have been temporarily extended. Pharmacists are permitted to provide medication management reviews via telehealth. A Home Medicines Service has been introduced to facilitate delivery of medications to people who are vulnerable or elderly. Anticipatory prescribing and medication imprest systems are valuable for access to end-of-life medications within residential aged care.

Design and Characterization of Injectable Poly(Lactic-Co-Glycolic Acid) Pastes for Sustained and Local Drug Release.

PURPOSE: We describe the preparation of injectable polymeric paste (IPP) formulations for local and sustained release of drugs. Furthermore, we include the characterization and possible applications of such pastes. Particular attention is paid to characteristics relevant to the successful clinical formulation development, such as viscosity, injectability, degradation, drug release, sterilization, stability performance and pharmacokinetics. METHODS: Paste injectability was characterized using measured viscosity and the Hagen-Poiseuille equation to determine injection forces. Drug degradation, release and formulation stability experiments were performed in vitro and drug levels were quantified using HPLC-UV methods. Pharmacokinetic evaluation of sustained-release lidocaine IPPs used five groups of six rats receiving increasing doses subcutaneously. An anti-cancer formulation was evaluated in a subcutaneous tumor xenograft mouse model. RESULTS: The viscosity and injectability of IPPs could be controlled by changing the polymeric composition. IPPs demonstrated good long-term stability and tunable drug-release with low systemic exposure in vivo in rats. Preliminary data in a subcutaneous tumor model points to a sustained anticancer effect. CONCLUSIONS: These IPPs are tunable platforms for local and sustained delivery of drugs and have potential for further clinical development to treat a number of diseases.

A polymeric paste-drug formulation for intratumoral treatment of prostate cancer.

OBJECTIVE: Focal therapy has emerged as a treatment option for low- to intermediate-risk localized prostate cancer (PCa) patients, to balance the risks for urinary and sexual morbidity of radical treatment with the psychological burden of active surveillance. In this context, we developed ST-4PC, an injectable, polymeric paste formulation containing docetaxel (dtx) and bicalutamide (bic) for image-guided focal therapy of PCa. The objective of this work was to evaluate the in vitro characteristics and in vivo toxicity and efficacy of ST-4PC. MATERIAL AND METHODS: In vitro drug release was evaluated using high-performance liquid chromatography. In vivo toxicity of blank- and drug-loaded ST-4PC was assessed in mice and rats. Tumor growth inhibition was evaluated in LNCaP subcutaneous (s.c.) and LNCaP-luc orthotopic xenograft models. Using the s.c. model, mice were monitored weekly for weight loss, tumor volume (TV) and serum PSA. For the orthotopic model, mice were additionally monitored for bioluminescence as measure of tumor growth. RESULTS: ST-4PC demonstrated a sustained and steady release of incorporated drugs with 50% dtx and 20% bic being released after 14 days. While no systemic toxicity was observed, dose-dependent local side effects from dtx developed in the s.c. but not in the orthotopic model, illustrating the limitations of s.c. models for evaluating local cytotoxic therapy. In the s.c. model, 0.1%/4% and 0.25%/4% dtx/bic ST-4PC paste significantly reduced PSA progression, but did not have a significant inhibitory effect on TV. ST-4PC loaded with 1%/4% dtx/bic significantly reduced TV, serum PSA, and bioluminescence in the orthotopic xenograft model. Compared with drugs dissolved in DMSO, ST-4PC significantly delayed tumor growth. CONCLUSION: Image-guided focal therapy using ST-4PC demonstrated promising inhibition of PSA progression and orthotopic tumor growth in vivo without significant toxicity, and warrants further clinical evaluation.

Temperature affects acute mayfly responses to elevated salinity: implications for toxicity of road de-icing salts.

Salinity in freshwater ecosystems has increased significantly at numerous locations throughout the world, and this increase often reflects the use or production of salts from road de-icing, mining/oil and gas drilling activities, or agricultural production. When related to de-icing salts, highest salinity often occurs in winter when water temperature is often low relative to mean annual temperature at a site. Our study examined acute (96 h) responses to elevated salinity (NaCl) concentrations at five to seven temperature treatments (5-25°C) for four mayfly species (Baetidae: Neocloeon triangulifer, Procloeon fragile; Heptageniidae: Maccaffertium modestum; Leptophlebiidae: Leptophlebia cupida) that are widely distributed across eastern North America. Based on acute LC50s at 20°C, P. fragile was most sensitive (LC50 = 767 mg l-1, 1447 µS cm-1), followed by N. triangulifer (2755 mg l-1, 5104 µS cm-1), M. modestum (2760 mg l-1, 5118 µS cm-1) and L. cupida (4588 mg l-1, 8485 µS cm-1). Acute LC50s decreased as temperature increased for all four species (n = 5-7, R2 = 0.65-0.88, p = 0.052-0.002). Thus, acute salt toxicity is strongly temperature dependent for the mayfly species we tested, which suggests that brief periods of elevated salinity during cold seasons or in colder locations may be ecologically less toxic than predicted by standard 20 or 25°C laboratory bioassays.This article is part of the theme issue 'Salt in freshwaters: causes, ecological consequences and future prospects'.

Enhanced taxane uptake into bladder tissues following co-administration with either mitomycin C, doxorubicin or gemcitabine: association to exfoliation processes.

OBJECTIVE: To investigate the effect of three anticancer drugs (mitomycin c (MMC), doxorubicin or gemcitabine) on bladder wall morphology and the uptake of paclitaxel or docetaxel following coadministration. The primary objective of this study was to measure the uptake of MMC, doxorubicin or gemcitabine with or without exposure of the tissue to amine terminated cationic nanoparticles (CNPs) and to investigate any possible exfoliation effects of the three drugs on intact bladder tissue. The secondary objective was to investigate the uptake of taxane drugs (docetaxel, DTX) and paclitaxel, (PTX) from surfactant micelle formulations in the presence of MMC, doxorubicin or gemcitabine. MATERIALS AND METHODS: Sections of fresh pig bladder tissue were incubated in Franz diffusion cells with the urothelial side exposed to solutions of doxorubicin, MMC and gemcitabine containing radioactive drug for 90 min. Some tissue samples were simultaneously exposed to each of the three drugs in combination with the surfactant micelle formulations of PTX (Taxol) or DTX (Taxotere). Tissue sections were then cryostat sectioned for drug quantitation by liquid scintillation counting or fixed for scanning electron microscopy and haematoxylin and eosin staining. RESULTS: All three drugs caused exfoliation of the urothelial layer of bladder tissues. Drug uptake studies showed that all three drugs effectively penetrated the lamina propria through to the muscular layer over a 2-h incubation and these levels were unaffected by pre-treatment with CNPs. The uptake levels of the taxane drugs PTX and DTX were significantly enhanced following simultaneous treatment of bladders with MMC, doxorubicin or gemcitabine. CONCLUSION: The exfoliation effects of MMC, doxorubicin and gemcitabine allow for good tissue penetration of these drugs with no additional effect from CNP treatment of bladders. The observed exfoliation effect of these amine-containing drugs probably arises from a cationic interaction with the mucus and urothelium cell layer in a manner similar to that previously reported for CNPs. These studies suggest that the lack of long-term clinical efficacy of these drugs may not arise from poor intravesical drug penetration but may result from a rapid diffusion of the drugs into the deeper vascularised muscular region with rapid drug clearance. The enhanced uptake of PTX or DTX following co-administration with MMC, doxorubicin or gemcitabine probably arises from the removal of the urothelial barrier by exfoliation allowing for improved taxane partitioning into superficial layers. These effects may allow for dual drug intravesical strategies offering greatly improved taxane uptake and potential additive drug effects for improved efficacy.

Magnetically-actuated drug delivery device (MADDD) for minimally invasive treatment of prostate cancer: An in vivo animal pilot study.

BACKGROUND: The vast majority of prostate cancer presents clinically localized to the prostate without evidence of metastasis. Currently, there are several modalities available to treat this particular disease. Despite radical prostatectomy demonstrating a modest prostate cancer specific mortality benefit in the PIVOT trial, several novel modalities have emerged to treat localized prostate cancer in patients that are either not eligible for surgery or that prefer an alternative approach. METHODS: Athymic nude mice were subcutaneously inoculated with prostate cancer cells. The mice were divided into four cohorts, one cohort untreated, two cohorts received docetaxel (10 mg/kg) either subcutaneously (SC) or intravenously (IV) and the fourth cohort was treated using the magnetically-actuated docetaxel delivery device (MADDD), dispensing 1.5 µg of docetaxel per 30 min treatment session. Treatment in all three therapeutic arms (SC, IV, and MADDD) was administered once weekly for 6 weeks. Treatment efficacy was measured once a week according to tumor volume using ultrasound. In addition, calipers were used to assess tumor volume. RESULTS: Animals implanted with the device demonstrated no signs of distress or discomfort, neither local nor systemic symptoms of inflammation and infection. Using an independent sample t-test, the tumor growth rate of the treated tumors was significant when compared to the control. Post hoc Tukey HSD test results showed that the mean tumor growth rate of our device cohort was significantly lower than SC and control cohorts. Moreover, IV cohort showed slight reduction in mean tumor growth rates than the ones from the device cohort, however, there was no statistical significance in tumor growth rate between these two cohorts. Furthermore, immunohistochemistry demonstrated an increased cellular apoptosis in the MADDD treated tumors and a decreased proliferation when compared to the other cohorts. In addition, IV cohort showed increased treatment side effects (weight loss) when compared to the device cohort. Finally, MADDD showed minimal expression of CD45 comparable to the control cohort, suggesting no signs of chronic inflammation. CONCLUSIONS: In conclusion, this study showed for the first time that MADDD, clearly suppressed tumor growth in local prostate cancer tumors. This could potentially be a novel clinical treatment approach for localized prostate cancer.

Physiological responses to short-term thermal stress in mayfly (Neocloeon triangulifer) larvae in relation to upper thermal limits.

Understanding species' thermal limits and their physiological determinants is critical in light of climate change and other human activities that warm freshwater ecosystems. Here, we ask whether oxygen limitation determines the chronic upper thermal limits in larvae of the mayfly Neocloeon triangulifer, an emerging model for ecological and physiological studies. Our experiments are based on a robust understanding of the upper acute (∼40°C) and chronic thermal limits of this species (>28°C, ≤30°C) derived from full life cycle rearing experiments across temperatures. We tested two related predictions derived from the hypothesis that oxygen limitation sets the chronic upper thermal limits: (1) aerobic scope declines in mayfly larvae as they approach and exceed temperatures that are chronically lethal to larvae; and (2) genes indicative of hypoxia challenge are also responsive in larvae exposed to ecologically relevant thermal limits. Neither prediction held true. We estimated aerobic scope by subtracting measurements of standard oxygen consumption rates from measurements of maximum oxygen consumption rates, the latter of which was obtained by treating with the metabolic uncoupling agent carbonyl cyanide-4-(trifluoromethoxy) pheylhydrazone (FCCP). Aerobic scope was similar in larvae held below and above chronic thermal limits. Genes indicative of oxygen limitation (LDH, EGL-9) were only upregulated under hypoxia or during exposure to temperatures beyond the chronic (and more ecologically relevant) thermal limits of this species (LDH). Our results suggest that the chronic thermal limits of this species are likely not driven by oxygen limitation, but rather are determined by other factors, e.g. bioenergetics costs. We caution against the use of short-term thermal ramping approaches to estimate critical thermal limits (CTmax) in aquatic insects because those temperatures are typically higher than those that occur in nature.

Identification of major factors in Australian primary care pharmacists' practice environment that have a bearing on the implementation of professional models of practice.

Objective The aim of the present study was to describe an environmental framework for pharmacists in primary care in Australia and determine the major factors within that environment that have the greatest bearing on their capacity to implement patient-focused models of professional practice. Methods A draft framework for pharmacists' practice was developed by allocating structures, systems and related factors known to the researchers or identified from the literature as existing within pharmacists' internal, operational and external environments to one of five domains: Social, Technological, Economic, Environmental or Political [STEEP]. Focus groups of pharmacists used an adapted nominal group technique to assess the draft and add factors where necessary. Where applicable, factors were consolidated into groups to establish a revised framework. The three major factors or groups in each domain were identified. The results were compared with the enabling factors described in the profession's vision statement. Results Seventy-eight individual factors were ultimately identified, with 86% able to be grouped. The three dominant groups in each of the five domains that had a bearing on the implementation of professional models of practice were as follows: (1) Social: the education of pharmacists, their beliefs and the capacity of the pharmacist workforce; (2) Technological: current and future practice models, technology and workplace structures; (3) Economic: funding of services, the viability of practice and operation of the Pharmaceutical Benefits Scheme; (4) Environmental: attitudes and expectations of stakeholders, including consumers, health system reform and external competition; and (5) Political: regulation of practice, representation of the profession and policies affecting practice. Conclusions The three dominant groups of factors in each of the five STEEP environmental domains, which have a bearing on pharmacists' capacity to implement patient-focused models of practice, correlate well with the enabling factors identified in the profession's vision statement, with the addition of three factors in the Environmental domain of stakeholder attitudes, health system reform and external competition. What is known about the topic? The extensive range of patient-focused professional programs developed for application by pharmacists in primary care in Australia has yet to be widely implemented. What does this paper add? Factors both within and beyond the pharmacists' immediate practice environment that have a bearing on the uptake of professional programs have been identified and prioritised using a structured thematic approach. What are the implications for practitioners? The results demonstrate the need for a multifactorial approach to the implementation of professional models of practice in this setting.

The Effective Solubilization of Hydrophobic Drugs Using Epigallocatechin Gallate or Tannic Acid-Based Formulations.

Hydrotropic solubilization of hydrophobic drugs requires supramolar amounts of hydrotropes with potential toxicity issues. We investigated the use of epigallocatechin gallate (EGCG) and tannic acid at millimolar concentrations, as hydrotrope-like solubilizing agents. Paclitaxel, docetaxel, amphotherecin B, curcumin, or rapamycin were dried down with EGCG or tannic acid from ethanol and then redissolved in aqueous media. Following centrifugation and filtration, the drug solubility was measured using HPLC. The uptake of docetaxel into cells from EGCG-based solutions was measured using radiolabeled drugs. Both EGCG and tannic acid effectively increased the aqueous solubility of all drugs from low levels (µg/mL) to high levels (mg/mL) in a concentration-dependent fashion at millimolar concentrations. Solutions were generally stable at room temperature over 24 h. Compared with micellar formulations, EGCG-based solutions of docetaxel demonstrated markedly improved drug uptake or transport levels in all cell lines. The use of these additives may provide improved formulation of various hydrophobic drugs using oral, parenteral, localized, or device-associated delivery systems.

Development of a nanofibrous wound dressing with an antifibrogenic properties in vitro and in vivo model.

Dermal fibrosis, characterized by excessive extracellular matrix (ECM), is a pathological condition with limited effective therapeutic modalities. Lack of an antiscarring dressing further impedes the preventive measures for this condition. Here, we develop a new antiscarring dressing and investigate its potential as a slow-releasing vehicle for kynurenic acid (KynA), an antifibrotic agent. KynA was incorporated into polymethyl methacrylate (PMMA) nanofibers, containing increasing concentration of polyethylene glycol (PEG). Fibre morphology, water absorption capacity, surface hydrophilicity, in vitro drug release profile, and in vivo antifibrotic effects were investigated. Increasing concentrations of PEG (1-20%) significantly increased surface hydrophilicity, water absorption capacity, and drug release. Based on the obtained release profiles, PMMA + 10% PEG was the preferred formulation for sustained KynA release up to 120 hours. In vitro studies confirmed the preservation of KynA antifibrotic properties during electrospinning, indicated by fibroblasts proliferation suppression and ECM expression modulation. In vivo application of KynA-incorporated films significantly inhibited collagen (23.89 ± 4.79 vs. 6.99 ± 0.41, collagen-I/ß-actin mRNA expression, control vs. treated) and fibronectin expression (7.18 ± 1.09 vs. 2.31 ± 0.05, fibronectin/ß-actin mRNA expression, control vs. treated) and enhanced the production of an ECM-degrading enzyme (2.03 ± 0.88 vs. 11.88 ± 1.16 MMP-1/ß-actin mRNA expression, control vs. treated). The fabricated KynA-incorporated films can be exploited as antifibrotic wound dressings. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2334-2344, 2016.