Lexley Maureen Pinto Pereira

Background/Objectives: Bacteria are becoming increasingly resistant to levofloxacin and other fluoroquinolones. Previously, drug loading in colloidal carriers has shown enhanced penetration into and retention in bacterial cells. However, the mechanism of levofloxacin niosomes’ bio-disposition in rats has not been reported. This study investigated the pharmacokinetics (PK) of optimized levofloxacin niosomes following intraperitoneal injection into Sprague Dawley rats. Methods: Formulation and processing variables settings were determined using DoE Fusion One software. The resulting data input into the Optimizer module provided niosome formulation for in vivo study in Sprague Dawley rats. Each group of rats (n = 6) was injected intraperitoneally with either conventional levofloxacin or its niosomes at equivalent doses of 7.5 mg/kg/dose. Blood samples were collected via tail snip and analyzed using a validated HPLC method. The plasma–time data were fed into the Gastroplus software (Simulations Plus, CA) and used to model levofloxacin PK. Results: Niosomes for in vivo study had a mean hydrodynamic diameter of 329.16 nm (±18.0), encapsulation efficiency (EE) of 30.74%, Zeta potential of 21.72 (±0.54), and polydispersity index (PDI) of 0.286 (±0.014). Both the Akaike and Schwarz criteria showed levofloxacin niosomes and conventional drug formulation obeying one- and two-compartment PK models, respectively. Thus, formulation in niosomes altered levofloxacin biodistribution by concentrating the drug in the vascular compartment. Conclusions: Niosome encapsulation of levofloxacin altered its biodistribution and pharmacokinetic profile, possibly by protecting i.p. levofloxacin en route into plasma, and significantly enhanced its plasma concentration with enhanced potential for treating intravascular infections.

This study investigated the pharmacokinetics of levofloxacin niosomes following a single dose administered intraperitoneally to Sprague Dawley rats, using conventional unentrapped drug as reference. Guided by results of previous studies, an experimental design software (DoE Fusion One) was used to design screening experiments that provided factor combinations and processing variable settings that resulted in an optimized formulation. Optimized niosomes of levofloxacin were prepared, characterized and evaluated in vitro for drug release rate. The well-characterized formulation was used for in vivo study in Sprague Dawley rats in a non-cross over parallel study. One of two groups of rats (n = 6 each) was injected intraperitoneally with conventional levofloxacin and the other with levofloxacin niosomes at 7.5mg/kg/dose. Blood samples were collected at ½, 1, 2, 4, 8, 12, 18, 24, 48 and 72 hours via tail snip. Drug concentrations were determined using a validated high-performance liquid chromatographic (HPLC) method. The plasma concentration versus time data from rats were fed into the Gastroplus software (Simulations Plus, CA) and used to model the pharmacokinetic profiles of the i.p. levofloxacin and its niosomes. The optimized drug-loaded niosomes used for in vivo rat study had a mean size of 368.8 (± 11.0 SE), encapsulation efficiency (EE) of 34.21 %, Zeta potential of -42.10 (± 2.07 SE) and mean polydispersity index (PDI) of 0.316 (± 0.014 SE). Following i.p. injection, levofloxacin release was controlled with less than 80 % released in 6 h and about 90% released in 12 h. Modeling of levofloxacin bio-disposition following i.p. injection in rats with Akaike information criterion (AIC) and Schwarz criterion (SC) indicated that the niosomes formulations are best fitted to one-compartment model while the conventional drug formulation followed two-compartment model. The niosomal formulation appeared to alter the biodistribution of levofloxacin, and concentrated the drug in the vascular compartment with slow, sustained distribution outside of the vascular compartment. Overall, the niosomes formulation showed significant increase in levofloxacin mean residence time (MRT), prolonged its elimination half-life (t1/2) and decrease its volume of distribution (Vd). Encapsulation of levofloxacin in niosomes altered its pharmacokinetic profile. It appears that, by vesicular encapsulation, niosomes altered levofloxacin biodistribution possibly by preventing its binding to plasma protein while correspondingly increasing its residence time in systemic circulation. Thus, by protecting intraperitoneally injected levofloxacin en route into the plasma, niosomes significantly enhance its delivery to, and concentration in, the intravascular compartment with enanced potential for treating intravascular conditions like bacteremia.

Objective: This study assessed recommendations for asthma care that community pharmacists in Trinidad offer to adult and adolescent asthma patients. Methods: A convenience study was conducted in community pharmacies in Trinidad, utilising a 17-question survey, delivered electronically via email by clicking a survey link, which ensured that all responses were anonymous. Key findings: There were 210 responses, and the majority (54.2%) believed that inhaled salbutamol was the treatment for mild intermittent asthma. Many (65.2%) demonstrate inhaler technique to new patients. Recommendations for using peak flow metres (46.2%) or asthma diaries (48.6%) were poor, and 68.1% dispense prednisolone without a prescription. Conclusion: Continuing education on asthma management for community pharmacists in Trinidad can optimise disease outcomes and make them partners in patient care.

This study examined the effectiveness of niosomes loaded with levofloxacin in treating Pseudomonas aeruginosa (American Type Culture Collection—ATCC 27853) infections in Sprague Dawley rats since these infections are becoming more common and resistant to treatment. Levofloxacin entrapped in niosomes was prepared using the thin-film hydration method and was assessed for in vitro release and stability. Three groups of six (6) animals were infected with a lethal dose of Pseudomonas aeruginosa via the intraperitoneal (Ip) route. At six (6) hours postinfection, the animals were treated with either drug-free niosomes (control), free levofloxacin (conventional), or levofloxacin trapped in niosomes (Ip) at a dose of 7.5 mg/kg/once daily. Blood was collected via tail snips on days 0, 1, 3, 5, 7, and 10 for complete blood counts and viable bacterial counts (CFU/μl). At day 10, the animals were sacrificed, and the kidney, liver, and spleen were harvested for bacterial counts. The niosomes showed a sustained drug release profile and were most stable at 4°C. All animals in the control group succumbed to the infection; one animal from the conventional group died, and all niosome treated animals survived at day 10. The mean lymphocyte count (×10⁹) was lower for the niosome (7.258 ± 1.773) versus conventional group (17.684 ± 10.008) ( ) at day ten (10). Neutrophil counts (×10⁹) were lower for the niosome (2.563 ± 1.609) versus conventional (6.2 ± 6.548) ( ) groups. Though CFUs in the bloodstream were comparable for both treatment groups, the niosome treated group showed a significant reduction of CFUs in the liver, kidney, and spleen versus the conventional group (1.33 ± 2.074) vs (5.8 ± 3.74) ( ), (1.5 ± 2.35) vs (9.6 ± 8.65) ( ) and (3.8 4.71) vs (25.6 14.66) ( ), respectively. These findings indicate that niosome is promising as a drug delivery system in treating systemic infections, but further work using niosomes with surface modification is recommended.

OBJECTIVE Asthma, a major cause of disability and reduced quality of life, has a high global prevalence and burden of death. Despite the propitious guidelines, a substantial portion of asthmatics reportedly have poorly controlled disease. In the current study, we have examined risk factors for uncontrolled asthma in specialty clinics and its association with impaired quality of life. METHODS A multicentre cross-sectional survey of asthma patients, 18 years and older, was conducted in Trinidad. Asthma Control Test (ACT) and the Juniper Mini Asthma Quality of Life Questionnaire (Mini AQLQ–J) were used to assess the disease control and quality of life, respectively. Data were analyzed using the Chi-square test and multivariable logistic regression controlling for gender. RESULTS Of a total of 428 patients included, asthma was uncontrolled in 72.4% and asthma related quality of life was moderate to severely impaired in 86% of the studied population. In the multivariate regression models, poorly controlled asthma was associated with obesity (OR 2.25; 95% CI 1.30-3.39), late-onset asthma (OR 1.72; 95% CI 1.04-2.84), features of sleep apnea (OR 1.77; 95% CI 1.01-3.07) and depression (OR 2.01; 95% CI 1.04-3.86). Impaired quality of life was associated with Indo-Caribbean ethnicity (OR 3.19; 95% CI = 1.68-6.06). CONCLUSIONS In this Caribbean population, uncontrolled asthma was independently associated with obesity, late-onset disease, and comorbidities of sleep apnea and depression. Poor asthma-related quality of life was independently associated with Indo-Caribbean ethnicity.

Currently, evidence concerning electronic cigarette (e-cigarette) use in the West Indies is unavailable. This study examines the prevalence and associated factors of e-cigarette use in young Trinidadian adults, 6 years after e-cigarettes were introduced in Trinidad. Young adults between the ages of 18 and 40 years were surveyed from May–June 2016. Based on the survey results, descriptive statistics and logistic regression models were used to identify correlations in e-cigarette use. The prevalence of those who had used e-cigarettes was 24.6%, and 41.9% of these people had used both e-cigarettes and tobacco cigarettes. A high proportion (16.95%) of those who had never used tobacco cigarettes had used e-cigarettes. Males were twice as likely as females to have used e-cigarettes (odds ratio [OR]: 2.60; 95% confidence interval [CI]: 1.85–3.68), and participants aged 18–25 years were more likely than those aged 36–40 years to use e-cigarettes (OR: 0.37; 95% CI: 0.14–0.81). The predictors of e-cigarette use as assessed by univariate analysis were current tobacco cigarette smoking (OR: 9.34; 95% CI: 6.14–14.39; p<0.001) and the belief that e-cigarettes are dangerous to health (OR: 0.61; 95% CI: 0.44–0.85; p=0.004). The predictors as assessed by multivariate logistic regression (adjusted OR) were ethnicity (p=0.043), education (p=0.012), and age group (p=0.007). Those who quit using tobacco cigarettes were 7.98 times more likely to use e-cigarettes (95% CI: 4.21–15.45), and those who knew that e-cigarettes contain nicotine were 2.70 times more likely to use them (95% CI: 1.53–4.86; p<0.001). Two summative scales were constructed that measured knowledge and perception. The perception scale, but not the knowledge scale (Cronbach’s alpha=0.736), was a significant predictor of e-cigarette use. The number of e-cigarette users is high (24.6%) in young adults in Trinidad and in those who have never smoked tobacco (16.95%). Current smokers, as well as those who have quit smoking, are at an increased risk of e-cigarette use. This study established that young adults have a low level of knowledge regarding e-cigarettes and shows that they should be educated on e-cigarette use. Further research to examine the reasons for, and susceptibility to, e-cigarette use is necessary.

The aim of this study was to describe the level and perception of control in severe asthma in Trinidad after the introduction of revised guidelines for asthma management. Adult asthmatics ( N = 329) at Trinidad’s chest clinics were cross-sectionally examined for guideline-defined disease control. Patients’ mean (SD) age was 54.36 (14.9) years, with body mass index = 28.54 (7.4) kg/meter², and females were proportionally more (246, 74.74%). Measured (45.29%) and perceived (18.96%) uncontrolled disease were poorly concordant (κ statistic = 0.197). Co-morbidity (≥2 conditions) correlated with uncontrolled disease in 55.80% of patients (Spearman correlation p = 0.03). Absolute peak expiratory flow was higher ( p < 0.001) in controlled and/or partially controlled disease than in uncontrolled asthma. Routine work limitation, night-time disturbances, work absenteeism, exacerbations, rescue inhalation and perceived control correlated with uncontrolled asthma ( p < 0.001). Few patients self-monitored lung function (9.73%) or kept an asthma diary (6.69%), but 65.1% believed they had to live with their symptoms. The asthma burden was at least one hospitalization (53.80%) and emergency department visit (66.36%) in the past year, cough (74.49%), dyspnoea (84.50%), wheezing (80.55%) and chest tightness (66.87%). After the revised guidelines, uncontrolled asthma and related morbidity remain suboptimal, with disagreeing actual and perceived control. Efforts to transform guidelines into patient care with realistic interpretation of control are recommended.

Restrictive pulmonary deficit is associated with inflammation in suboptimally controlled obese diabetics