Pharmacist interventions in osteoporosis management: a systematic review.

Internationally, there is an osteoporosis treatment gap, which pharmacists may assist in closing. This review identifies pharmacist interventions for improving osteoporosis management and evaluates their effectiveness. Pharmacist interventions are shown to improve osteoporosis management in terms of increasing investigation and treatment commencement and osteoporosis therapy adherence. INTRODUCTION: This review identifies pharmacist interventions for improving osteoporosis management and evaluates their effectiveness. METHODS: A literature search using PubMed, Embase, International Pharmaceutical Abstracts, and Cumulative Index to Nursing and Allied Health Literature was undertaken from database inception to June 2022. Randomised controlled trials were eligible, if they included adults diagnosed with or at risk of osteoporosis and assessed pharmacist interventions to improve osteoporosis management. Outcomes regarding investigation, treatment, adherence and patient knowledge were evaluated using qualitative analysis. The quality of included studies was assessed using the Critical Appraisal Skills Programme checklists and the Cochrane Collaboration tool to assess the risk of bias (Rob 2.0). RESULTS: Sixteen articles (12 different studies) with a total of 16,307 participants, published between 2005 and 2018 were included. Pharmacist interventions were classified into two categories, those targeting investigation and treatment (n = 10) and those targeting adherence (n = 2). The impact of the intervention on patient knowledge was considered by studies targeting both investigation and treatment (n = 2) and adherence (n = 1). Pharmacist interventions demonstrated benefit for all outcomes; however, the extent to which conclusions can be drawn on their effectiveness is limited by the heterogeneity of interventions employed and methodological issues identified. Patient education and counselling were identified as a cornerstone of pharmacist interventions targeting both investigation and treatment and adherence, along with the importance of pharmacist and physician collaboration. CONCLUSION: Pharmacist interventions show promise for improving osteoporosis management. The potential for pharmacists to contribute to closing the osteoporosis treatment gap through undertaking population screening has been identified.

Co-design and feasibility of a pharmacist-led minor ailment service.

BACKGROUND: Community pharmacies provide an appropriate setting to deliver minor ailment services (MASs). Many community pharmacy services have been developed previously without stakeholder involvement. As a result, implementation of services may fail to produce the expected impact. The aim of this research was to co-design and test the feasibility of an Australian MAS for minor ailment presentations. METHODS: This study used co-design methodology which included two phases: (1) a focus group with stakeholders to allow the conceptualization of the service and agreement on service elements; (2) a literature review of clinical guidelines and three working meetings with a team of editors and general practitioners for the development of treatment pathways. Following this, a study evaluating the feasibility of the co-designed service was undertaken. The qualitative part of the methodology associated with the feasibility study comprised semi-structured interviews with MAS pharmacists, observation and completion of a tool by change facilitators identifying barriers and facilitators to service delivery. Qualitative data obtained for all phases were analysed using thematic analysis. RESULTS: The developed service included the following components: (i) an in-pharmacy consultation between the patient and pharmacist, (ii) treatment pathways accessible to pharmacists on the internet to guide consultations, (iii) existing digital communication systems used by general practice to exchange patient information, (iv) training, and (v) change facilitation. As a result of feasibility testing, twenty-six implementation factors were identified for practice change, with the main change being the simplification of the pharmacist-patient consultation and data collection processes. CONCLUSIONS: An Australian MAS was generated as a result of co-design, while testing revealed that the co-designed service was feasible. As a result of integrating the views of multiple stakeholders, the designed MAS has been adapted to suit healthcare practices, which may increase the acceptance and impact of MAS when implemented into practice.

Cost utility of a pharmacist-led minor ailment service compared with usual pharmacist care.

BACKGROUND: A cluster randomised controlled trial (cRCT) performed from July 2018 to March 2019 demonstrated the clinical impact of a community pharmacist delivered minor ailment service (MAS) compared with usual pharmacist care (UC). MAS consisted of a technology-based face-to-face consultation delivered by trained community pharmacists. The consultation was guided by clinical pathways for assessment and management, and communication systems, collaboratively agreed with general practitioners. MAS pharmacists were trained and provided monthly practice support by a practice change facilitator. The objective of this study was to assess the cost utility of MAS, compared to UC. METHODS: Participants recruited were adult patients with symptoms suggestive of a minor ailment condition, from community pharmacies located in Western Sydney. Patients received MAS (intervention) or UC (control) and were followed-up by telephone 14-days following consultation with the pharmacist. A cost utility analysis was conducted alongside the cRCT. Transition probabilities and costs were directly derived from cRCT study data. Utility values were not available from the cRCT, hence we relied on utility values reported in the published literature which were used to calculate quality adjusted life years (QALYs), using the area under the curve method. A decision tree model was used to capture the decision problem, considering a societal perspective and a 14-day time horizon. Deterministic and probabilistic sensitivity analyses assessed robustness and uncertainty of results, respectively. RESULTS: Patients (n = 894) were recruited from 30 pharmacies and 82% (n = 732) responded to follow-up. On average, MAS was more costly but also more effective (in terms of symptom resolution and QALY gains) compared to UC. MAS patients (n = 524) gained an additional 0.003 QALYs at an incremental cost of $7.14 (Australian dollars), compared to UC (n = 370) which resulted in an ICER of $2277 (95% CI $681.49-3811.22) per QALY. CONCLUSION: Economic findings suggest that implementation of MAS within the Australian context is cost effective.Trial registration Registered with Australian New Zealand Clinical Trials Registry (ANZCTR) and allocated the ACTRN: ACTRN12618000286246. Registered on 23 February 2018.

Use of over-the-counter laxatives by community-dwelling adults to treat and prevent constipation: a national cross-sectional study.

PURPOSE: Constipation is commonly self-managed with over-the-counter laxatives. The study aim was to explore laxative choice, healthcare professional recommendations in laxative selection, and laxative effectiveness when laxatives are used for treatment and for prevention of constipation by community-dwelling adults. METHODS: A nationally representative sample of community-dwelling adults in Australia was surveyed. Participants completed an online questionnaire. Z tests for differences in proportions were used to compare the proportion of laxatives by class when used either for treatment or for prevention of constipation by choice of laxative, healthcare professional recommendation, and perceived effectiveness. RESULTS: The questionnaire was completed by 2024 participants. Laxatives were used by 37% (n = 747) of participants with 31.3% using laxatives for treatment, 19.3% for prevention, and 49.7% using laxatives for both purposes. The most common laxatives used for treatment and prevention were contact laxatives (39.8% and 31.1% respectively) and bulk-forming laxatives (34.3% and 44.6% respectively). Of all laxatives used, 56.4% of laxatives were chosen with healthcare professional recommendation, and 53.5% of laxatives were found effective. CONCLUSION: Laxatives were used both for treatment and for prevention of constipation. However, laxatives are often perceived to be ineffective and healthcare professionals are not always involved in laxative choice. Modified guidelines which address the use of laxatives for both treatment and prevention, and increased healthcare professional involvement in appropriate choice and use of laxatives, may be required to improve constipation management in the community.

Letter to the Editor: Integrating the Roles of Pharmacy Practice and Drug Delivery in Mitigating COVID-19.

No Abstract Available.

Chronic Constipation in the Community: A National Survey of Australian Adults.

PURPOSE: The aim of this study was to determine the prevalence of chronic constipation and identify factors associated with chronic constipation in community-dwelling adults. DESIGN: Cross-sectional study. METHODS: The target population was community-dwelling Australian adults; 1978 participants completed an online questionnaire exploring symptoms, management, and factors potentially associated with constipation. Chronic constipation was identified using Rome III criteria. Multivariate logistic regression model was used to identify factors associated with chronic constipation. RESULTS: The prevalence of chronic constipation was 23.9%. Factors significantly associated with chronic constipation in the multivariate model were female gender (odds ratio [OR] = 1.42, 95% confidence interval [CI], 1.12-1.81), current employment (OR = 1.45, 95% CI, 1.11-1.88), regular smoking (OR = 1.60, 95% CI, 1.19-2.14), poor self-rated health (OR = 2.57, 95% CI, 1.28-5.19), thyroid disease (OR = 1.77, 95% CI, 1.21-2.79), depression (OR = 1.49, 95% CI, 1.08-2.06), hemorrhoids (OR = 2.98, 95% CI, 1.84-4.83), irritable bowel syndrome (OR = 2.45, 95% CI, 1.73-3.46), and use of anti-inflammatory/antirheumatic medications (OR = 2.06, 95% CI, 1.15-3.68). In contrast to these factors, use of medications acting on the renin-angiotensin system was associated with a reduced likelihood of chronic constipation (OR = 0.47, 95% CI, 0.24-0.91). CONCLUSIONS: Chronic constipation is prevalent among community-dwelling adults. Various factors associated with chronic constipation have been identified, and knowledge of these factors may help health care professionals recognize individuals who are at high risk of chronic constipation.

Defining constipation to estimate its prevalence in the community: results from a national survey.

BACKGROUND: Different definitions of constipation have been used to estimate its prevalence in the community but this creates difficulties when comparing results from various studies. This study explores the impact of different definitions on prevalence estimates in the same population and compares the performance of simple definitions with the Rome III criteria. METHODS: The prevalence of constipation in a large nationally representative sample of community-dwelling adults was estimated using five simple definitions of constipation and compared with definitions based on the Rome III criteria. The sensitivity, specificity, and positive and negative predictive values, were calculated for each definition using the Rome III criteria as the gold standards for chronic and sub-chronic constipation. RESULTS: Prevalence estimates for the five simple definitions ranged from 9.4 to 58.9%, while the prevalence estimates using the Rome III criteria were 24.0% (95%CI: 22.1, 25.9) for chronic constipation and 39.6% (95%CI: 37.5, 41.7) for sub-chronic constipation. None of the simple definitions were adequate compared to the Rome III criteria. Self-reported constipation over the past 12 months had the highest sensitivity (91.1%, 95%CI: 88.8, 93.4) and negative predictive value (94.5%, 95%CI: 93.1, 96.1) compared to the Rome III criteria for chronic constipation but an unacceptably low specificity (51.3%, 95%CI: 48.8, 53.8) and positive predictive value (37.1%, 95%CI: 34.4, 39.9). CONCLUSIONS: The definition used to identify constipation within a population has a considerable impact on the prevalence estimate obtained. Simple definitions, commonly used in research, performed poorly compared with the Rome III criteria. Studies estimating population prevalence of constipation should use definitions based on the Rome criteria where possible.

Laxative Use and Self-Reported Constipation in a Community-Dwelling Elderly Population: A Community-Based Survey From Australia.

The objectives of this study were to (1) determine the prevalence of laxative use and self-reported constipation and (2) identify risk factors associated with constipation in a community-dwelling elderly population. A retrospective cross-sectional survey using data from the Australian Longitudinal Study of Ageing was used to explore laxative use and constipation in a cohort of community-dwelling older persons. The prevalence of laxative use was 15% and the prevalence of self-reported constipation was 21%. Females were more likely to report constipation and use laxatives. Of those using laxatives, men were more likely to have their laxatives prescribed by a doctor whereas women were more likely to self-medicate. Poor self-rated health and a higher need for assistance with activities of daily living were identified as risk factors for constipation. Constipation is a common condition affecting the community-dwelling elderly. There is a need to optimize the management of constipation and use of laxatives in such populations.

Pharmacists' views on implementing a disease state management program for low back pain.

Pharmacists have the potential to take a lead role in the primary care management of people with acute low back pain. The aim of this study was to investigate pharmacists' views on implementing a care program for people with acute low back pain in the community pharmacy. Recruitment of pharmacists for this study took place between July 2012 and March 2013. A convenience sample of 30 pharmacists who collaborated in recruiting participants for a low back pain clinical trial in Sydney (n=15 pharmacist recruiters and n=15 non-recruiters) completed an open-ended questionnaire. There was no marked variation in responses between the two groups. Participating pharmacists were receptive to the idea of implementing a care program for people with low back pain, highlighting the need for adequate reimbursement and adequate training of staff to ensure it is successful. Pharmacists identified that the follow up of people receiving such a service is dependent on several factors such as effective reminder systems and the proximity of patients to the pharmacy.

Naturally acquired antibodies against Haemophilus influenzae type a in Aboriginal adults, Canada.

In the post-Haemophilus influenzae type b (Hib) vaccine era that began in the 1980's, H. influenzae type a (Hia) emerged as a prominent cause of invasive disease in North American Aboriginal populations. To test whether a lack of naturally acquired antibodies may underlie increased rates of invasive Hia disease, we compared serum bactericidal activity against Hia and Hib and IgG and IgM against capsular polysaccharide between Canadian Aboriginal and non-Aboriginal healthy and immunocompromised adults. Both healthy and immunocompromised Aboriginal adults exhibited significantly higher bactericidal antibody titers against Hia than did non-Aboriginal adults (p = 0.042 and 0.045 respectively), with no difference in functional antibody activity against Hib. IgM concentrations against Hia were higher than IgG in most study groups; the inverse was true for antibody concentrations against Hib. Our results indicate that Aboriginal adults possess substantial serum bactericidal activity against Hia that is mostly due to IgM antibodies. The presence of sustained IgM against Hia suggests recent Hia exposure.

Knowledge and satisfaction of pharmacists attending an educational workshop on evidence-based management of low back pain.

Pharmacists are well positioned to provide quality care to people with low back pain (LBP). Education and training can equip pharmacists with the knowledge to optimally manage LBP in primary care. The aim of this study was to investigate the knowledge and satisfaction of pharmacists who attended a 2-h educational workshop on the evidence-based management of LBP. Case-based learning, underpinned by key adult learning principles, was one teaching method used to deliver important educational messages. Knowledge was assessed using a questionnaire consisting of multiple-choice, true/false questions and a written vignette based on a real-life clinical case scenario. Written feedback from pharmacists was used to gauge the success and limitations of the intervention. One hundred and ninety-three pharmacists completed the in-house assessment. Pharmacists demonstrated an accurate understanding of evidence-based pharmacological management of LBP, with all identifying paracetamol as the first-line drug choice for non-specific LBP. Ninety-nine per cent of pharmacists identified the symptoms presented in the vignette as a syndrome representing a significant clinical red flag requiring urgent referral. This educational intervention has delivered key messages on LBP management to pharmacists. There is a continued need for educational interventions addressing common conditions.

Osteoporosis management in Australian aged care facilities: a mixed method study.

Osteoporosis is a common but sub-optimally managed disease amongst aged care residents. Pharmacists undertaking comprehensive medication reviews is one strategy to improve osteoporosis management. Analysis of pharmacist medication review recommendations has identified common clinical practice issues that can be addressed to optimise osteoporosis management for aged care residents. PURPOSE: This study investigates the prevalence of osteoporosis medicine use amongst Australian aged care residents and explores drug-related problems (DRPs) identified during medication reviews and pharmacist recommendations to resolve them. METHODS: Resident demographics, medications, diagnoses, osteoporosis related DRPs, and recommendations to resolve them were extracted from medication review reports. A mixed methods approach was taken to analysis, involving descriptive statistical analysis and content analysis. RESULTS: Medication review reports relating to 980 residents were collected. Antiresorptive therapies were used by 21.7% of residents, of which 87.2% were prescribed denosumab. Osteoporosis related DRPs represented 14.0% of all DRPs identified by pharmacists. Vitamin D was involved in 55.4% of these DRPs, the remainder concerned antiresorptive therapies (23.4%), medications contributing to osteoporosis (16.3%), and calcium (4.9%). Frequent deviations in practice from aged care clinical guidelines and consensus recommendations concerning vitamin D and calcium were found. DRPs and accompanying recommendations relating to denosumab revealed inadequate monitoring and inadvertent therapy disruptions. CONCLUSION: Pharmacist identified DRPs and recommendations revealed common aspects of clinical practice that can be addressed to improve osteoporosis management for aged care residents. A need to raise awareness of aged care-specific consensus recommendations concerning vitamin D and calcium is evident. Facility protocols and procedures must be developed and implemented to ensure safe and effective use of denosumab.

Relationship between medication safety-related processes and medication use in residential aged care facilities.

OBJECTIVE: To explore the association between the implementation of medication safety-related processes measured with the Medication Safety Self-Assessment for Long-Term Care (MSSA-LTC) tool and medication use in residential aged care facilities (RACFs). METHODS: A descriptive cross-sectional study was conducted in Australian RACFs. Data on facility characteristics, aggregated medication use at the facility level for selected medications commonly associated with a high risk of harm and the MSSA-LTC were completed by clinical pharmacists providing clinical pharmacy services. The Spearman's correlation test was used to evaluate the association between the MSSA-LTC score and medication use. A scatter plot between the MSSA-LTC score and medication use data was generated, and a linear trend line was plotted using the least squares method. RESULTS: Data were collected from 31 RACFs servicing 2986 residents. Most medication safety-related processes were implemented in Australian RACFs. A higher facility MSSA-LTC score was associated with a lower proportion of residents with polypharmacy (r = -.48, p = .01) and one or more benzodiazepines (r = -.41, p = .03). In addition, a negative linear trend was observed between the MSSA-LTC score and the average number of medications per resident, the proportion of residents with one or more anticonvulsants and the proportion of residents using one or more opioid analgesics. CONCLUSIONS: This study indicates that implementing medication safety-related processes may improve medication use in RACFs.

Exploring the influence of the microbiome on the pharmacology of anti-asthmatic drugs.

The microbiome is increasingly implicated in playing a role in physiology and pharmacology; in this review, we investigate the literature on the possibility of bacterial influence on the pharmacology of anti-asthmatic drugs, and the potential impact this has on asthmatic patients. Current knowledge in this area of research reveals an interaction between the gut and lung microbiome and the development of asthma. The influence of microbiome on the pharmacokinetics and pharmacodynamics of anti-asthmatic drugs is limited; however, understanding this interaction will assist in creating a more efficient treatment approach. This literature review highlighted that bioaccumulation and biotransformation in the presence of certain gut bacterial strains could affect drug metabolism in anti-asthmatic drugs. Furthermore, the bacterial richness in the lungs and the gut can influence drug efficacy and could also play a role in drug response. The implications of the above findings suggest that the microbiome is a contributing factor to an individuals' pharmacological response to anti-asthmatic drugs. Hence, future directions for research should follow investigating how these processes affect asthmatic patients and consider the role of the microbiome on drug efficacy and modify treatment guidelines accordingly.

Decoding epilepsy treatment: A comparative evaluation contrasting cannabidiol pharmacokinetics in adult and paediatric populations.

Epilepsy is a neurological disorder characterized by overstimulation of neurotransmitters and uncontrolled seizures. Current medications for epilepsy result in adverse effects or insufficient seizure control, highlighting the necessity to develop alternative therapies. Cannabidiol (CBD), derived from cannabis plants, has been popularly explored as an alternative. CBD is shown to have anti-convulsivatng and muscle-relaxing properties, which have been used in patients with epilepsy with promising results. Current research explores varying dosages in either adult or paediatric patients, with little or no comparison between the two populations. In this review, we aim at consolidating this data and comparing the effect and pharmacokinetic properties of CBD across these two patient populations. When comparing the absorption, there was insufficient data to show differences between paediatric and adult patients. Similarly, limited information was available in comparing the distribution of CBD, but a higher volume of distribution was found in the paediatric population. From the metabolism perspective, the paediatric population had a greater success rate when treated with the drug compared to the adult population. In the elimination, there were no clear distinctions in the clearance rate between the two populations. The drug's half-life was highly variable in both populations, with paediatrics having a lower range than adults. In summary, the paediatric population had a more significant reduction in the severity of seizures compared to the adult population upon CBD treatment. The complexity in which CBD operates highlights the need for further studies of the compound to further understand why differences occur between these two populations.

Comparative pharmacokinetic evaluation of nanoparticle-based vs. conventional pharmaceuticals containing statins in attenuating dyslipidaemia.

Dyslipidaemia describes the condition of abnormal lipid levels in a person's bloodstream. Since the 1980s, statin medications have been used to treat dyslipidaemia and other comorbidities, such as stroke risk and atherosclerosis. Statin medications were initially synthesised from fungal metabolites, but many synthetic statin drugs have been manufactured since then. Statin medication is quite effective in reducing total cholesterol levels in the bloodstream, but it has limitations. Due to their poor water solubility, statin drugs possess poor oral bioavailability, which hinders their therapeutic efficacy. Nanoparticle drug delivery technology has been shown to improve the pharmacokinetic profiles of many drug classes, and statins have great potential to benefit from this. This paper reviewed the currently available literature on nanoparticle statin medication and evaluated the possible improvements that can be made to the pharmacokinetic profile and efficacy of conventional statin medication. It was found that the oral bioavailability of nanoparticle medication consistently outperformed conventional medication by up to 400% in some cases. Substantial improvements in time to peak plasma concentration and plasma concentration peaks were also found, and increased periods in circulation before excretion were shown. It was concluded that nanoparticle technology has the potential to completely replace conventional statin medication as it offers more significant benefits with minimal drawbacks. Upon further study and development, the manufacture of nanoparticle statin medication should become feasible enough for large-scale application, which will significantly benefit patients and unburden healthcare systems.

Investigation of smoking on the antiplatelet response to clopidogrel: Unravelling the smoker's paradox.

The intricate relationship between smoking and the effects of the antiplatelet drug clopidogrel has been termed the "smoker's paradox". This paradox details the enhanced efficacy of clopidogrel in smokers compared to non-smokers. This review begins with an exploration of the proposed mechanisms of the smoker's paradox, particularly drawing attention to the induction of cytochrome P450 (CYP) isoenzymes via tobacco smoke, specifically the enzymes CYP1A2 and CYP2C19. Moreover, an investigation of the effects of genetic variability on the smoker's paradox was undertaken from both clinical and molecular perspectives, delving into the effects of ethnicity and genetic polymorphisms. The intriguing role of CYP1A2 genotypes and the response to clopidogrel in smoking and non-smoking populations was examined conferring insight into the individuality rather than universality of the smoker's paradox. CYP1A2 induction is hypothesised to elucidate the potency of smoking in exerting a counteracting effect in those taking clopidogrel who possess CYP2C19 loss of function polymorphisms. Furthermore, we assess the comparative efficacies of clopidogrel and other antiplatelet agents, namely prasugrel and ticagrelor. Studies indicated that prasugrel and ticagrelor provided a more consistent effect and further reduced platelet reactivity compared to clopidogrel within both smoking and non-smoking populations. Personalised dosing was another focus of the review considering patient comorbidities, genetic makeup, and smoking status with the objective of improving the antiplatelet response of those taking clopidogrel. In summation, this review provides insight into multiple areas of research concerning clopidogrel and the smoker's paradox taking into account proposed mechanisms, genetics, other antiplatelet agents, and personalised dosing.

Revolutionizing lung health: Exploring the latest breakthroughs and future prospects of synbiotic nanostructures in lung diseases.

The escalating prevalence of lung diseases underscores the need for innovative therapies. Dysbiosis in human body microbiome has emerged as a significant factor in these diseases, indicating a potential role for synbiotics in restoring microbial equilibrium. However, effective delivery of synbiotics to the target site remains challenging. Here, we aim to explore suitable nanoparticles for encapsulating synbiotics tailored for applications in lung diseases. Nanoencapsulation has emerged as a prominent strategy to address the delivery challenges of synbiotics in this context. Through a comprehensive review, we assess the potential of nanoparticles in facilitating synbiotic delivery and their structural adaptability for this purpose. Our review reveals that nanoparticles such as nanocellulose, starch, and chitosan exhibit high potential for synbiotic encapsulation. These offer flexibility in structure design and synthesis, making them promising candidates for addressing delivery challenges in lung diseases. Furthermore, our analysis highlights that synbiotics, when compared to probiotics alone, demonstrate superior anti-inflammatory, antioxidant, antibacterial and anticancer activities. This review underscores the promising role of nanoparticle-encapsulated synbiotics as a targeted and effective therapeutic approach for lung diseases, contributing valuable insights into the potential of nanomedicine in revolutionizing treatment strategies for respiratory conditions, ultimately paving the way for future advancements in this field.

Zerumbone-incorporated liquid crystalline nanoparticles inhibit proliferation and migration of non-small-cell lung cancer in vitro.

Lung cancer is the second most prevalent type of cancer and is responsible for the highest number of cancer-related deaths worldwide. Non-small-cell lung cancer (NSCLC) makes up the majority of lung cancer cases. Zerumbone (ZER) is natural compound commonly found in the roots of Zingiber zerumbet which has recently demonstrated anti-cancer activity in both in vitro and in vivo studies. Despite their medical benefits, ZER has low aqueous solubility, poor GI absorption and oral bioavailability that hinders its effectiveness. Liquid crystalline nanoparticles (LCNs) are novel drug delivery carrier that have tuneable characteristics to enhance and ease the delivery of bioactive compounds. This study aimed to formulate ZER-loaded LCNs and investigate their effectiveness against NSCLC in vitro using A549 lung cancer cells. ZER-LCNs, prepared in the study, inhibited the proliferation and migration of A549 cells. These inhibitory effects were superior to the effects of ZER alone at a concentration 10 times lower than that of free ZER, demonstrating a potent anti-cancer activity of ZER-LCNs. The underlying mechanisms of the anti-cancer effects by ZER-LCNs were associated with the transcriptional regulation of tumor suppressor genes P53 and PTEN, and metastasis-associated gene KRT18. The protein array data showed downregulation of several proliferation associated proteins such as AXL, HER1, PGRN, and BIRC5 and metastasis-associated proteins such as DKK1, CAPG, CTSS, CTSB, CTSD, and PLAU. This study provides evidence of potential for increasing the potency and effectiveness of ZER with LCN formulation and developing ZER-LCNs as a treatment strategy for mitigation and treatment of NSCLC.

Zerumbone liquid crystalline nanoparticles protect against oxidative stress, inflammation and senescence induced by cigarette smoke extract in vitro.

The purpose of this study was to evaluate the potential of zerumbone-loaded liquid crystalline nanoparticles (ZER-LCNs) in the protection of broncho-epithelial cells and alveolar macrophages against oxidative stress, inflammation and senescence induced by cigarette smoke extract in vitro. The effect of the treatment of ZER-LCNs on in vitro cell models of cigarette smoke extract (CSE)-treated mouse RAW264.7 and human BCi-NS1.1 basal epithelial cell lines was evaluated for their anti-inflammatory, antioxidant and anti-senescence activities using colorimetric and fluorescence-based assays, fluorescence imaging, RT-qPCR and proteome profiler kit. The ZER-LCNs successfully reduced the expression of pro-inflammatory markers including Il-6, Il-1ß and Tnf-α, as well as the production of nitric oxide in RAW 264.7 cells. Additionally, ZER-LCNs successfully inhibited oxidative stress through reduction of reactive oxygen species (ROS) levels and regulation of genes, namely GPX2 and GCLC in BCi-NS1.1 cells. Anti-senescence activity of ZER-LCNs was also observed in BCi-NS1.1 cells, with significant reductions in the expression of SIRT1, CDKN1A and CDKN2A. This study demonstrates strong in vitro anti-inflammatory, antioxidative and anti-senescence activities of ZER-LCNs paving the path for this formulation to be translated into a promising therapeutic agent for chronic respiratory inflammatory conditions including COPD and asthma.