Liposomal curcumin inhibits cigarette smoke induced senescence and inflammation in human bronchial epithelial cells.

Curcumin, the principal curcuminoid of turmeric (Curcuma longa extract), is very well known for its multiple biological therapeutic activities, particularly its anti-inflammatory and antioxidant potential. However, due to its low water solubility, it exhibits poor bioavailability. In order to overcome this problem, in the current study, we have employed liposomal technology to encapsulate curcumin with the aim of enhancing its therapeutic efficacy. The curcumin-loaded liposomes (PlexoZome®) were tested on a cigarette smoke extract-induced Chronic Obstructive Pulmonary Disease (COPD) in vitro model using minimally immortalized human bronchial epithelial cells (BCiNS1.1). The anti-senescence and anti-inflammatory properties of PlexoZome® were explored. 5 µM PlexoZome® curcumin demonstrated anti-senescent activity by decrease in X-gal positive cells, and reduction in the expression of p16 and p21 in immunofluorescence staining. Moreover, PlexoZome® curcumin also demonstrated a reduction in proteins related to senescence (osteopontin, FGF basic and uPAR) and inflammation (GM-CSF, EGF and ST2). Overall, the results clearly demonstrate the therapeutic potential of curcumin encapsulated liposomes in managing CSE induced COPD, providing a new direction to respiratory clinics.

18-ß-glycyrrhetinic acid-loaded polymeric nanoparticles attenuate cigarette smoke-induced markers of impaired antiviral response in vitro.

Tobacco smoking is a leading cause of preventable mortality, and it is the major contributor to diseases such as COPD and lung cancer. Cigarette smoke compromises the pulmonary antiviral immune response, increasing susceptibility to viral infections. There is currently no therapy that specifically addresses the problem of impaired antiviral response in cigarette smokers and COPD patients, highlighting the necessity to develop novel treatment strategies. 18-ß-glycyrrhetinic acid (18-ß-gly) is a phytoceutical derived from licorice with promising anti-inflammatory, antioxidant, and antiviral activities whose clinical application is hampered by poor solubility. This study explores the therapeutic potential of an advanced drug delivery system encapsulating 18-ß-gly in poly lactic-co-glycolic acid (PLGA) nanoparticles in addressing the impaired antiviral immunity observed in smokers and COPD patients. Exposure of BCi-NS1.1 human bronchial epithelial cells to cigarette smoke extract (CSE) resulted in reduced expression of critical antiviral chemokines (IP-10, I-TAC, MIP-1α/1ß), mimicking what happens in smokers and COPD patients. Treatment with 18-ß-gly-PLGA nanoparticles partially restored the expression of these chemokines, demonstrating promising therapeutic impact. The nanoparticles increased IP-10, I-TAC, and MIP-1α/1ß levels, exhibiting potential in attenuating the negative effects of cigarette smoke on the antiviral response. This study provides a novel approach to address the impaired antiviral immune response in vulnerable populations, offering a foundation for further investigations and potential therapeutic interventions. Further studies, including a comprehensive in vitro characterization and in vivo testing, are warranted to validate the therapeutic efficacy of 18-ß-gly-PLGA nanoparticles in respiratory disorders associated with compromised antiviral immunity.

Curcumin-loaded liposomes modulating the synergistic role of EpCAM and estrogen receptor alpha in lung cancer management.

Lung cancer (LC) remains a leading cause of cancer-related mortality worldwide, necessitating the exploration of innovative therapeutic strategies. This study delves into the in vitro potential of liposomal therapeutics utilizing Curcumin-loaded PlexoZome® (CUR-PLXZ) in targeting EpCAM/TROP1 and Estrogen Receptor Alpha (ERα) signalling pathways for LC management. The prevalence of LC, particularly non-small cell lung cancer (NSCLC), underscores the urgent need for effective treatments. Biomarkers like EpCAM/TROP1 and ERα/NR3A1 play crucial roles in guiding targeted therapies and influencing prognosis. EpCAM plays a key role in cell-cell adhesion and signalling along with ERα which is a nuclear receptor that binds estrogen and regulates gene expression in response to hormonal signals. In LC, both often get overexpressed and are associated with tumour progression, metastasis, and poor prognosis. Curcumin, a phytochemical with diverse therapeutic properties, holds promise in targeting these pathways. However, its limited solubility and bioavailability necessitate advanced formulations like CUR-PLXZ. Our study investigates the biological significance of these biomarkers in the A549 cell line and explores the therapeutic potential of CUR-PLXZ, which modulates the expression of these two markers. An in vitro analysis of the A549 human lung adenocarcinoma cell line identified that CUR-PLXZ at a dose of 5 µM effectively inhibited the expression of EpCAM and ERα. This finding paves the way for targeted intervention strategies in LC management.

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.

Ribavirin attenuates carcinogenesis by downregulating IL-6 and IL-8 in vitro in human lung adenocarcinoma.

Lung cancer is one of the leading causes of death worldwide, whereby the major contributing factors are cigarette smoking and exposure to environmental pollutants. Despite the availability of numerous treatment options, including chemotherapy, the five-year survival rate is still extremely low, highlighting the urgent need to develop novel, more effective therapeutic strategies. In this context, the repurposing of previously approved drugs is an advantage in terms of time and resources invested. Ribavirin is an antiviral drug approved for the treatment of hepatitis C, which shows potential for repurposing as an anticancer agent. Among the many signaling molecules promoting carcinogenesis, the interleukins (ILs) IL-6 and IL-8 are interesting therapeutic targets as they promote a variety of cancer hallmarks such as cell proliferation, migration, metastasis, and angiogenesis. In the present study, we show that ribavirin significantly downregulates the expression of IL-6 and IL-8 in vitro in A549 human lung adenocarcinoma cells. The results of this study shed light on the anticancer mechanisms of ribavirin, providing further proof of its potential as a repurposed drug for the treatment of lung cancer.

Dosing challenges in respiratory therapies.

The pulmonary route of administration has been commonly used for local lung conditions such as asthma and chronic obstructive pulmonary disease (COPD). Recently, with the advent of new technologies available for both formulation and device design, molecules usually delivered at high doses, such as antibiotics and insulin to treat cystic fibrosis (CF) and diabetes, respectively, can now be delivered by inhalation as a dry powder. These molecules are generally delivered in milligrams instead of traditional microgram quantities. High dose delivery is most commonly achieved via dry powder inhalers (DPIs), breath activated devices designed with a formulated powder containing micronized drug with aerodynamic diameters between 1 and 5 µm. The powder formulation may also contain other excipients and/or carrier particles to improve the flowability and aerosol dispersion of the powder. A drawback with high doses is that the formulation contains a great number of fine particles, leading to a greater degree of cohesive forces, producing strongly bound agglomerates. With greater cohesive forces holding fine particles together, higher dispersion forces are needed for efficient de-agglomeration and aerosolisation. This requirement of greater dispersion forces has led to different dry powder formulations and vastly different inhaler designs. The purpose of this review is to evaluate the different formulation types, various DPI devices currently available, and how these affect the aerosolisation process and delivery of high dosed inhalable dry powder formulations to the lungs.