Real change or more of the same? Analysing Australian media's portrayal of intellectual disability during the NDIS rollout.

BACKGROUND: Through the filtering of information, the creation, and reinforcement of stereotypes, media moulds attitudes and set agendas on critical social issues including public policy and disability. METHODS: This study explored Australian media representations of the care of people with intellectual disability during a crucial period in disability policy change: the National Disability Insurance Scheme (NDIS) rollout (2013-2018). Search criteria identified 168 news stories, examined via content analysis and news framing. RESULTS: Four major issues were identified: Roles and responsibilities of government; housing; mistreatment of persons with intellectual disability, and responsibility of care for families. Stories tended to be presented negatively, however, regional and local/community metropolitan stories were more balanced or positive compared with major metropolitan stories. CONCLUSION: Despite significant disability policy change, media presentations continue to reinforce stereotypes of people with intellectual disability and position the government as one continuing to fall short in critical areas of funding, safety, and support.

Artemisone and Artemiside Are Potent Panreactive Antimalarial Agents That Also Synergize Redox Imbalance in Plasmodium falciparum Transmissible Gametocyte Stages.

The emergence of resistance toward artemisinin combination therapies (ACTs) by the malaria parasite Plasmodium falciparum has the potential to severely compromise malaria control. Therefore, the development of new artemisinins in combination with new drugs that impart activities toward both intraerythrocytic proliferative asexual and transmissible gametocyte stages, in particular, those of resistant parasites, is urgently required. We define artemisinins as oxidant drugs through their ability to oxidize reduced flavin cofactors of flavin disulfide reductases critical for maintaining redox homeostasis in the malaria parasite. Here we compare the activities of 10-amino artemisinin derivatives toward the asexual and gametocyte stages of P. falciparum parasites. Of these, artemisone and artemiside inhibited asexual and gametocyte stages, particularly stage V gametocytes, in the low-nanomolar range. Further, treatment of both early and late gametocyte stages with artemisone or artemiside combined with the pro-oxidant redox partner methylene blue displayed notable synergism. These data suggest that modulation of redox homeostasis is likely an important druggable process, particularly in gametocytes, and this finding thereby enhances the prospect of using combinations of oxidant and redox drugs for malaria control.

Formulation of Natural Oil Nano-Emulsions for the Topical Delivery of Clofazimine, Artemisone and Decoquinate.

PURPOSE: The aim of this study was to formulate nano-emulsions comprising natural oils and the active pharmaceutical ingredients (APIs) clofazimine (CLF), artemisone (ATM) and decoquinate (DQ) in order to determine effectiveness of the nano-emulsions for topical delivery of the APIs. The APIs alone do not possess suitable physicochemical properties for topical drug delivery. METHODS: Nano-emulsions were formulated with olive and safflower oils encapsulating the APIs. Skin diffusion and tape stripping studies were performed. By using the lactate dehydrogenase (LDH) assay, in vitro toxicity studies were carried out on immortalized human keratinocytes (HaCaT) cell line to determine cytotoxicities due to the APIs and the nano-emulsions incorporating the APIs. RESULTS: The nano-emulsions were effective in delivering the APIs within the stratum corneum-epidermis and the epidermis-dermis, were non-cytotoxic towards HaCaT cell lines (p < 0.05) and inhibited Mycobacterium tuberculosis in vitro. CONCLUSION: Natural oil nano-emulsions successfully deliver CLF, ATM and DQ and in principle could be used as supplementary topical treatment of cutaneous tuberculosis (CTB). Graphical Abstract ᅟ.

In vitro anti-cancer effects of artemisone nano-vesicular formulations on melanoma cells.

Artemisone is a 10-amino-artemisinin derivative that is markedly superior in vitro and in vivo to current artemisinins against malaria and also possesses antitumor activity. In seeking to capitalise on the last property, we have examined the encapsulation of artemisone in nano-vesicular niosomes and solid lipid nanoparticles, and have evaluated efficacies of the free and encapsulated artemisone against human melanoma A-375 cells and effects on human keratinocytes (HaCaT). Artemisone is successfully encapsulated into the nano-vesicles with encapsulation efficiencies of 67±6% and 79±5%, and with average particle sizes being 211±10nm and 295±18nm respectively. The formulations displayed highly selective cytotoxicity towards the melanoma cells with negligible toxicity towards the normal skin cells. The artemisone-loaded nano-vesicles almost completely inhibited the melanoma cells compared to the free drug. The results overall suggest a potentially more useful therapeutic strategy that needs to be evaluated for the treatment of melanoma and other cancers. FROM THE CLINICAL EDITOR: Apart from being an effective anti-malarial drug, a surprising action of artemisone also has antitumor activity. Nonetheless, its low water solubility and bioavailability has limited its clinical use. In this article, the authors enacapsulated artemisone in nano- vesicles and solid lipid nano-particles (SLNs). In-vitro studies confirmed the selective cytotoxicity towards melanoma cells. Further in-vivo and pre-clinical studies are awaited.

Penetration enhancing effects of selected natural oils utilized in topical dosage forms.

CONTEXT: Various natural products, including oils, have been utilized as penetration enhancers due to their "safety profiles". These oils contain fatty acids promoting skin permeability through lipid fluidization within the stratum corneum; and might therefore be able to effectively enhance transdermal drug delivery. OBJECTIVE: We investigated possible penetration enhancing properties of selected oils, utilizing flurbiprofen as marker compound in emulgel formulations. The formulations were compared to a liquid paraffin emulgel and a hydrogel to establish any significant penetration enhancing effects. METHODS: Gas chromatographic analysis of the natural oils was performed at ambient temperature to determine the fatty acid composition in each selected natural oils. Franz cell diffusion studies and tape stripping methods were employed to study delivery of the marker into, and through the skin. RESULTS: The following rank order for the emulgel flux-values was obtained: Hydrogel >>>> olive oil >> liquid paraffin >> coconut oil > grape seed oil >> Avocado oil ≥ Crocodile oil >> Emu oil. DISCUSSION: Results suggested that oils containing predominantly mono-unsaturated oleic acid, on average increased the flux of the marker to a larger extent than oils containing an almost even mixture of both mono- and poly-unsaturated fatty acids. Oils comprising saturated fatty acids (SFAs) with alkyl chains between C12 and C14, increased the marker flux to a higher extent than oils containing C16-C18 SFAs. Effects observed for branched fatty acids, however, did not vary significantly from effects for unbranched fatty acids with the same carbon chain length. CONCLUSION: Natural oils possess penetration enhancing effects.

Topical Delivery of 5-Fluorouracil from Pheroid™ Formulations and the In Vitro Efficacy Against Human Melanoma.

Drug delivery vehicles can influence the topical delivery and the efficacy of an active pharmaceutical ingredient (API). In this study, the influence of Pheroid™ technology, which is a unique colloidal drug delivery system, on the skin permeation and antimelanoma efficacy of 5-fluorouracil were investigated. Lotions containing Pheroid™ with different concentrations of 5-fluorouracil were formulated then used in Franz cell skin diffusion studies and tape stripping. The in vitro efficacy of 5-fluorouracil against human melanoma cells (A375) was investigated using a flow cytometric apoptosis assay. Statistically significant concentrations of 5-fluorouracil diffused into and through the skin with Pheroid™ formulations resulting in an enhanced in vitro skin permeation from the 4.0% 5-fluorouracil lotion (p < 0.05). The stratum corneum-epidermis and epidermis-dermis retained 5-fluorouracil concentrations of 2.31 and 6.69 µg/ml, respectively, after a diffusion study with the 4.0% Pheroid™ lotion. Subsequent to the apoptosis assay, significant differences were observed between the effect of 13.33 µg/ml 5-fluorouracil in Pheroid™ lotion and the effects of the controls. The results obtained suggest that the Pheroid™ drug delivery system possibly enhances the flux and delivery of 5-fluorouracil into the skin. Therefore, using Pheroid™ could possibly be advantageous with respect to topical delivery of 5-fluorouracil.

Social isolation rearing induces mitochondrial, immunological, neurochemical and behavioural deficits in rats, and is reversed by clozapine or N-acetyl cysteine.

Apart from altered dopamine (DA) function, schizophrenia displays mitochondrial and immune-inflammatory abnormalities, evidenced by oxidative stress, altered kynurenine metabolism and cytokine release. N-acetyl cysteine (NAC), an antioxidant and glutamate modulator, is effective in the adjunctive treatment of schizophrenia. Social isolation rearing (SIR) in rats is a valid neurodevelopmental animal model of schizophrenia. This study evaluated whether SIR-induced behavioural deficits may be explained by altered plasma pro- and anti-inflammatory cytokines, kynurenine metabolism, and cortico-striatal DA and mitochondrial function (via adenosine triphosphate (ATP) release), and if clozapine or NAC (alone and in combination) reverses these changes. SIR induced pronounced deficits in social interactive behaviours, object recognition memory, and prepulse inhibition (PPI), while simultaneously increasing striatal but reducing frontal cortical accumulation of ATP as well as DA. SIR increased pro- vs. anti-inflammatory cytokine balance and altered kynurenine metabolism with a decrease in neuroprotective ratio. Clozapine (5mg/kg/day×14days) as well as clozapine+NAC (5mg/kg/day and 150mg/kg/day×14days) reversed these changes, with NAC (150mg/kg/day) alone significantly but partially effective in some parameters. Clozapine+NAC was more effective than clozapine alone in reversing SIR-induced PPI, mitochondrial, immune and DA changes. In conclusion, SIR induces mitochondrial and immune-inflammatory changes that underlie cortico-striatal DA perturbations and subsequent behavioural deficits, and responds to treatment with clozapine or NAC, with an additive effect following combination treatment. The data provides insight into the mechanisms that might underlie the utility of NAC as an adjunctive treatment in schizophrenia.

N-Acetyl cysteine reverses social isolation rearing induced changes in cortico-striatal monoamines in rats.

Schizophrenia is causally associated with early-life environmental stress, implicating oxidative stress in its pathophysiology. N-acetyl cysteine (NAC), a glutathione precursor and antioxidant, is emerging as a useful agent in the adjunctive treatment of schizophrenia and other psychiatric illnesses. However, its actions on brain monoamine metabolism are unknown. Social isolation rearing (SIR) in rats presents with face, predictive and construct validity for schizophrenia. This study evaluated the dose-dependent effects of NAC (50, 150 and 250 mg/kg/day × 14 days) on SIR- vs. socially reared induced changes in cortico-striatal levels of dopamine (DA), serotonin (5-HT) noradrenaline (NA) and their associated metabolites. SIR induced significant deficits in frontal cortical DA and its metabolites, 3,4-dihydroxyphenylacetic acid (Dopac) and homovanillic acid (HVA), reduced 5-HT and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), and reduced levels of the NA metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG). In addition, significant elevations in frontal cortical NA and striatal DA, Dopac, HVA, 5-HT, 5-HIAA, NA and MHPG were also observed in SIR rats. NAC at 150 and 250 mg/kg reversed all cortico-striatal DA, Dopac, HVA, 5-HT, 5-HIAA and striatal NA alterations in SIR animals, with 250 mg/kg of NAC also reversing alterations in cortico-striatal MHPG. In conclusion, SIR profoundly alters cortico-striatal DA, 5-HT and NA pathways that parallel observations in schizophrenia, while these changes are dose-dependently reversed or abrogated by sub-chronic NAC treatment. A modulatory action on cortico-striatal monoamines may explain NACs' therapeutic use in schizophrenia and possibly other psychiatric disorders, where redox dysfunction or oxidative stress is a causal factor.

A Systematic Literature Review of the Career Choice of Helping Professionals Who Have Experienced Cumulative Harm as a Result of Adverse Childhood Experiences.

The pervasive effects of cumulative harm resulting from adverse childhood experiences influence all aspects of an individual's life course. Research highlights a relationship between early trauma and career choice; however, there is a dearth of research pertaining specifically to cumulative harm and the influence on career choice in the helping professions. A systematic literature review was conducted to explore the associations of cumulative harm and childhood trauma on career decision making in people in the helping professions. A search was conducted across databases between February 1990 and February 2019 relevant to searches combining three areas of interest: (a) "childhood trauma," (b) "career choice," and (c) "helping professionals." Database searches and further manual searches yielded a total of 208 articles, and 28 studies satisfied all inclusion criteria. Only studies that were peer-reviewed and published between February 1990 and February 2019 were included. The evidence from the review indicated that family of origin dysfunction, parentification, individual characteristics, and traits developed through adversity, and experiential motivations were associated with the career choice in the helping professions. Further research is required to explore different professional cohorts and the utility of life themes as both a source of data for research and reflexive practice in helping professionals.

"I Want to Be Stepping in More" - Professional Online Forum Moderators' Experiences of Supporting Individuals in a Suicide Crisis.

Introduction: Individuals experiencing suicidal crises increasingly turn to online mental health forums for support. Support can come from peers but also from online moderators, many of whom are trained health professionals. Much is known about users' forum experiences; however, the experiences of professional moderators who work to keep users safe has been overlooked. The beneficial nature of online forums cannot be fully realized until there is a clearer understanding of both parties' participation. This study explored the experiences of professional online forum moderators engaged in suicide prevention. Materials and Methods: A purposive sample of professionally qualified moderators was recruited from three online mental health organizations. In-depth semi-structured, video-recorded interviews were conducted with 15 moderators (3 male, 12 female), to explore their experiences and perceptions of working in online suicide prevention spaces. Data was analyzed using inductive thematic analysis. Results: Five themes were identified related to the experiences and challenges for moderators. These were the sense of the unknown, the scope of the role, limitations of the written word, volume of tasks, and balancing individual vs. community needs. Discussion: Findings indicate that the professionally qualified moderator role is complex and multifaceted, with organizations failing to recognize these aspects. Organizations restrict moderators from using their full therapeutic skill set, limiting them to only identifying and re-directing at-risk users to crisis services. The benefits of moderated online forums could be enhanced by allowing moderators to use more of their skills. To facilitate this, in-situ research is needed that examines how moderators use their skills to identify at-risk users.

Survival estimates across five life stages of redfin (Perca fluviatilis) exposed to simulated pumped-storage hydropower stressors.

The global prevalence of pumped-storage hydropower (PSH) is expected to grow exponentially as countries transition to renewable energy sources. Compared to conventional hydropower, little is currently known regarding PSH impacts on aquatic biota. This study estimated the survival of five life stages (egg, two larval stages, juvenile and adult) of redfin (European) perch (Perca fluviatilis) following passage through a PSH facility during the pumping phase. This was achieved by simulating the individual stressors expected to occur during passage through a 2000-MW PSH facility using laboratory-simulated (shear strain and extreme compression) and modelling (blade strike, BS) approaches. Our results indicate that redfin could survive the shear, pressure and BS stressors expected within the PSH facility, but impacts varied among life stages. Juvenile survival was >70% across all shear strain rates, while the survival of eggs and larvae declined markedly as strain rate increased. All life stages had high survival when exposed to rapid compression and BS. The high survival of redfin to the stressors tested suggests the PSH facility could facilitate the passage of redfin during the pumping phase from the lower to the higher elevation reservoir. This outcome would be welcomed in situations where the species is native, but could have adverse implications for the conservation of native biota where the species is considered a pest.

Suicidal behaviours and moderator support in online health communities: a scoping review.

OBJECTIVES: Online support can be a crucial source of support for individuals experiencing suicidal behaviours, with forum moderators being pivotal in terms of the role they play in times of personal mental health emergencies. This study identified what is empirically known about the professional practices of health professionals who are online mental health forum moderators and provide support to individuals experiencing suicidal behaviours. DESIGN: The Levac, Colquhoun and O'Brien extension of the Arksey and O'Malley scoping review framework was used. SEARCH STRATEGY: The Psychology Collection (EBSCO), PsycINFO (EBSCO), Web of Science, Taylor and Francis Online, SAGE Journals and Science Direct databases were searched for articles that featured a result relating to an online forum; included participants who worked as online moderators or facilitators and focused on suicide or self-harm. Results were limited to peer-reviewed articles published in English from 1990 onwards. As a quality assurance measure, grey literature (nonacademic literature) was not included. Reference lists of included articles were hand-searched. RESULTS: There were 397 articles initially identified after applying inclusion and exclusion criteria, with five articles included for synthesis. All articles received a moderate quality rating. Only one article featured a moderator who was a qualified health professional; the moderators in the remaining articles were volunteers who undertook preservice training. We found that there is little research that examines the professional working practices of online moderators who support individuals experiencing suicidal behaviours. CONCLUSIONS: The dearth of research focusing on the professional practices of online forum moderators is cause for concern given that individuals experiencing suicidal behaviours are increasingly turning to online forums when in crisis. Future research should focus on online moderators' practice through interviewing moderators about their professional practices and by examining online moderator practice as it occurs in situ.

THE PULMONARY AND METABOLIC EFFECTS OF SUSPENSION BY THE FEET COMPARED WITH LATERAL RECUMBENCY IN IMMOBILIZED BLACK RHINOCEROSES (DICEROS BICORNIS) CAPTURED BY AERIAL DARTING.

Aerial translocation of captured black rhinoceroses (Diceros bicornis) has been accomplished by suspending them by their feet. We expected this posture would compromise respiratory gas exchange more than would lateral recumbency. Because white rhinoceroses (Ceratotherium simum) immobilized with etorphine alone are hypermetabolic, with a high rate of carbon dioxide production (VCO2), we expected immobilized black rhinoceroses would also have a high VCO2. Twelve (nine male, three female; median age 8 yr old [range: 4-25]; median weight 1,137 kg [range: 804-1,234] body weight) wild black rhinoceroses were immobilized by aerial darting with etorphine and azaperone. The animals were in lateral recumbency or suspended by their feet from a crane for approximately 10 min before data were collected. Each rhinoceros received both treatments sequentially, in random order. Six were in lateral recumbency first and six were suspended first. All animals were substantially hypoxemic and hypercapnic in both postures. When suspended by the feet, mean arterial oxygen pressure (PaO2) was 42 mm Hg, 4 mm Hg greater than in lateral recumbency (P=0.030), and arterial carbon dioxide pressure (PaCO2) was 52 mm Hg, 3 mm Hg less than in lateral recumbency (P=0.016). Tidal volume and minute ventilation were similar between postures. The mean VCO2 was 2 mL/kg/min in both postures and was similar to, or marginally greater than, VCO2 predicted allometrically. Suspension by the feet for 10 min did not impair pulmonary function more than did lateral recumbency and apparently augmented gas exchange to a small degree relative to lateral recumbency. The biological importance in these animals of numerically small increments in PaO2 and decrements in PaCO2 with suspension by the feet is unknown. Black rhinoceroses immobilized with etorphine and azaperone were not as hypermetabolic as were white rhinoceroses immobilized with etorphine.

Synthesis and transdermal permeation of novel N4-methoxypoly(ethylene glycol) carbamates of cytarabine.

BACKGROUND: Cytarabine is a deoxycytidine analogue commonly used in the treatment of hematological malignant diseases. Its clinical utility, however, is severely limited by its short plasma half-life because of the catabolic action of nucleoside deaminases. METHOD: In this study, N(4)-carbamate derivatives of cytarabine (1) were synthesized and evaluated for transdermal penetration because this mode of administration may circumvent its limitations. The synthesis of these compounds was achieved in a two-step process. First, the methoxypoly(ethylene glycol) was activated by p-nitrophenyl chloroformate. Second, the activated intermediates were reacted with cytarabine in the presence of N-hydroxysuccinamide to give the N(4)-methoxypoly(ethylene glycol) carbamate derivatives. The transdermal flux values of the N(4)-carbamates of cytarabine were determined in vitro by Franz diffusion cell methodology. Aqueous solubility and log D (pH 7.4) values were determined and assessed for correlation with transdermal flux values. RESULTS: The synthesized carbamates, particularly, (9)-(13), showed increased solubility in both aqueous and lipid media. Log D values decreased as the oxyethylene chain lengthened. CONCLUSION: Although none of the derivatives showed significantly higher transdermal penetration than cytarabine (1), it should be mentioned that the mean for cytarabine N(4)-methoxyethyleneoxycarbamate (8) was 10 times higher and the median was 2 times higher.

Suicidal behaviours and moderator support in online health communities: protocol for a scoping review.

INTRODUCTION: Suicidal ideation and suicidal behaviours are common yet complex mental health presentations that can pose significant challenges for health professionals. The inability to accurately predict the individuals who may move from experiencing suicidal ideation and associated behaviours, to completing suicide, presents one such challenge. This can make it difficult to provide interventions and support to those most in need. Online health communities are one possible source of support for individuals who experience suicidal ideation and behaviours. These communities are becoming an increasingly popular way of accessing support, often with life-saving consequences. Within online communities, support is offered by various individuals including, in some instances, health professionals from various backgrounds, who work as online health community moderators. Given the growth of online communities and the increasing number of health professionals working as moderators, this scoping review seeks to map the literature that has focused on health professionals working as online community moderators, who interact with members experiencing suicidal ideation and behaviours. Mapping the existing literature offers benefits to both research and practice by identifying gaps in the research and providing a beginning knowledge base of current practice that can inform the training and development of health professionals working as community moderators. METHODS AND ANALYSIS: This scoping review will follow the methodological framework of Arksey and O'Malley, later adapted by Levac et al. To ensure appropriate rigour, this protocol uses the 20-item Preferred Reporting Items for Systematic Reviews and Meta-Analyses and extension for Scoping Reviews. Literature will be identified using a search strategy developed in consultation with a specialist research librarian at the university where the researchers are employed. Ten multidisciplinary databases will be independently searched by two researchers, and both researchers will screen for inclusion, and undertake the data extraction. The first author will perform a quality assessment of the articles that are selected for inclusion. A second researcher will complete a random audit of 20% of the included articles to assess for quality and suitability in answering the research questions. The first author will complete the analysis and synthesis of the data. A numerical and narrative synthesis of the included studies will be provided. ETHICS AND DISSEMINATION: The scoping review has been deemed as being exempt from ethical review as no data will be collected from human participants. The results of the scoping review may be published in a peer-reviewed journal, thesis, presented at relevant conferences, and shared with relevant knowledge users.

Transport of aspalathin, a Rooibos tea flavonoid, across the skin and intestinal epithelium.

Since Rooibos tea contains high levels of flavonoid antioxidants with potential health benefits when taken orally or applied topically, the quantity of the antioxidants crossing the physiological barriers is of scientific, clinical and commercial importance. This study investigated the in vitro transport of aspalathin, a unique flavonoid constituent of Rooibos tea, across intestinal epithelial cells and the human skin. The transport studies were conducted for both pure aspalathin solutions and extracts from unfermented (or green) Rooibos (Aspalathus linearis) aerial plant material across human abdominal skin in vertical Franz diffusion cells and Caco-2 cell monolayers in Transwell 6-well plates. The results obtained from the percutaneous permeation studies demonstrated that only 0.01% of the initial aspalathin dose from both the test solution and extract permeated through the skin, which was in accordance with the prediction from its log P value of -0.347. A portion of 0.07% of the initial aspalathin dose penetrated the different layers of the skin for the green Rooibos extract solution and 0.08% for the pure aspalathin solution. The transport of aspalathin across Caco-2 cell monolayers was concentration dependent and reached almost 100% (P(app) = 20.93 x 10(-6) cm/s) of the initial dose in the highest concentration tested for the extract, while it was only 79.03% (P(app) = 15.34 x 10(-6) cm/s) of the initial dose for the highest concentration of the aspalathin solution.

Dermal delivery of selected hydrophilic drugs from elastic liposomes: effect of phospholipid formulation and surfactants.

The effect of phospholipid formulation and choice of surfactant on skin permeation of selected hydrophilic drugs from elastic liposomes across human epidermal membrane has been studied. Sodium cholate and various concentrations of phosphatidylcholine were used for the preparation of liposomes namely hydrogenated phosphatidylcholine 90% (Phospholipon 90H), phosphatidylcholine 95% (Phospholipon 90G), phosphatidylcholine 78.6% (Phospholipon 80), and phosphatidylcholine 50% (Phosal PG). To investigate the effect of the surfactant, liposomes were prepared from 95% phosphatidylcholine (Phospholipon 90G) and various surfactants (sodium cholate, sodium deoxycholate, Span 20 (sorbitan monolaurate), Span 40 (sorbitan monopalmitate), Span 60 (sorbitan stearate) and Span 80 (sorbitan monooleate)). The vesicles were prepared by the conventional rotary evaporation technique. The film was hydrated with phosphate-buffered saline (10 mL) containing 9, 2 and 2.5 mg mL(-1) of methotrexate, idoxuridine and aciclovir, respectively. All formulations contained 7% ethanol. Homogenously-sized liposomes were produced following extrusion through 100-nm polycarbonate filters using Lipex Extruder. Particle size was characterized by transmission electron microscopy. Vertical Franz diffusion cells were used for the study of drug delivery through human epidermal membrane. For the three drugs, the highest transcutaneous fluxes were from elastic liposomes containing 95% phosphatidylcholine. In general, a higher flux value was obtained for liposomes containing sodium cholate compared with sodium deoxycholate. For the liposomes containing sorbitan monoesters, there was no clearly defined trend between alkyl chain length and flux values. Overall, transcutaneous fluxes of liposomal preparations of hydrophilic drugs were comparable with those from saturated aqueous solutions (P > 0.05).

In vitro oral drug permeation models: the importance of taking physiological and physico-chemical factors into consideration.

INTRODUCTION: The assessment of intestinal membrane permeability properties of new chemical entities is a crucial step in the drug discovery and development process and a variety of in vitro models, methods and techniques are available to estimate the extent of oral drug absorption in humans. However, variations in certain physiological and physico-chemical factors are often not reflected in the results and the complex dynamic interplay between these factors is sometimes oversimplified with in vitro models. Areas covered: In vitro models to evaluate drug pharmacokinetics are briefly outlined, while both physiological and physico-chemical factors that may have an influence on these techniques are critically reviewed. The shortcomings identified for some of the in vitro techniques are discussed in conjunction with novel ways to improve and thereby overcome some challenges. Expert opinion: Although conventional in vitro methods and theories are used as basic guidelines to predict drug absorption, critical evaluations have identified some shortcomings. Advancements in technology have made it possible to investigate and understand the role of physiological and physico-chemical factors in drug delivery more clearly, which can be used to improve and refine the techniques to more closely mimic the in vivo environment.

Topical Delivery of Withania somnifera Crude Extracts in Niosomes and Solid Lipid Nanoparticles.

BACKGROUND: Withania somnifera is a medicinal plant native to India and is known to have anticancer properties. It has been investigated for its anti-melanoma properties, and since melanoma presents on the skin, it is prudent to probe the use of W. somnifera in topical formulations. To enhance topical drug delivery and to allow for controlled release, the use of niosomes and solid lipid nanoparticles (SLNs) as delivery vesicles were explored. OBJECTIVE: The objective of this study is to determine the stability and topical delivery of W. somnifera crude extracts encapsulated in niosomes and SLNs. MATERIALS AND METHODS: Water, ethanol, and 50% ethanol crude extracts of W. somnifera were prepared using 24 h soxhlet extraction which were each encapsulated in niosomes and SLNs. Franz cell diffusion studies were conducted with the encapsulated extracts to determine the release and skin penetration of the phytomolecules, withaferin A, and withanolide A. RESULTS: The niosome and SLN formulations had average sizes ranging from 165.9 ± 9.4 to 304.6 ± 52.4 nm with the 50% ethanol extract formulations having the largest size. A small particle size seemed to have correlated with a low encapsulation efficiency (EE) of withaferin A, but a high EE of withanolide A. There was a significant difference (P < 0.05) between the amount of withaferin A and withanolide A that were released from each of the formulations, but only the SLN formulations managed to deliver withaferin A to the stratum corneum-epidermis and epidermis-dermis layers of the skin. CONCLUSION: SLNs and niosomes were able to encapsulate crude extracts of W. somnifera and release the marker compounds, withaferin A, and withanolide A, for delivery to certain layers in the skin. SUMMARY: Withania somnifera crude extracts were prepared using ethanol, water, and 50% ethanol as solvents. These three extracts were then incorporated into niosomes and solid lipid nanoparticles (SLNs) for use in skin diffusion studies, thus resulting in six formulations (ethanol niosome, water niosome, 50% ethanol niosome, ethanol SLN, water SLN, and 50% ethanol SLN). The diffusion of two marker compounds (withaferin A and withanolide A) from the formulations into the skin was then determined. Abbreviations used: API: Active pharmaceutical ingredient, ANOVA: Analysis of variance, ED: Epidermis-dermis, HPLC: High-performance liquid chromatography, HLB: Hydrophilic-lipophilic balance, NMR: Nuclear magnetic resonance spectroscopy, PDI: Polydispersity index, SLN: Solid lipid nanoparticle, SD: Standard deviation, SCE: Stratum corneum-epidermis, TEM: Transmission electron microscopy.

In vitro wound healing and cytotoxic effects of sinigrin-phytosome complex.

Sinigrin is a class of glucosinolates found naturally in plants of the Brassicaceae family. Lately, studies have shown that sinigrin possesses anticancer, antibacterial and anti-inflammatory activities. Since its efficacy has not been explored on wound healing, we examined the effect of sinigrin on HaCaT cells. We also aimed at formulating sinigrin into phytosome to form a sinigrin-phytosome complex and study the wound healing and cytotoxic activities on A-375 and HaCaT cells. Sinigrin was efficiently formulated into the phytosome with an average particle size of 153 ± 39 nm, zeta potential of 10.09 ± 0.98 mV and complex efficiency of 69.5 ± 5%. The formation of the sinigrin-phytosome complex was confirmed by DSC and FTIR analysis. The sinigrin-phytosome complex significantly exhibited wound healing effects when compared to sinigrin alone. After 42 h, the phytosome complex completely healed the wound, whereas sinigrin alone showed only 71% wound closure. The sinigrin-phytosome complex displayed minimal toxicity towards HaCaT cells and at higher concentrations, it showed potent activity towards A-375. The results indicated that sinigrin-phytosome complex augmented the therapeutic potential of sinigrin towards the wound healing activity and this approach should be explored further for cancerous wound treatment.