Purpose: A simple, rapid, sensitive, and reliable HPLC method with UV detection was developed and validated for simultaneous quantitation of docetaxel and celecoxib and paclitaxel for dissolution characterization and pharmacokinetic studies. Methods: The HPLC assay was performed isocratically on a reversed-phase C18 μ-Bondapack column using a mobile phase of acetonitrile:water (45:55, v/v) at a flow rate of 1.2 mL/min, and the analytes were detected at 230 nm. Paclitaxel was used as an internal standard for analysis of plasma samples following simple liquid-liquid extraction with n-hexane:isoamyl alcohol (97:3). The method was validated for specificity, linearity, sensitivity, precision, accuracy, robustness, and in vitro-in vivo application. Results: The retention times for docetaxel, paclitaxel, and celecoxib were 10.94, 12.4, and 16.81 min, respectively. The standard curves covering 0.1-1 μg/mL and 0.05-4 μg/mL were linear using dissolution medium and rat plasma, respectively. The limit of quantitation of the method was 50 ng/mL using 100 μL of rat plasma sample and injection of 50 μL of the residue. Within- and between-day precision and accuracy did not exceed 16.86% and 12.10%, respectively. This validated method was successfully used to quantify docetaxel and celecoxib simultaneously in the release study of docetaxel-celecoxib -loaded porous microparticles and pharmacokinetics studies. The methods were found to be simple, specific, precise, accurate, and reproducible. In this study, paclitaxel was used as the internal standard while dexamethasone, flutamide, and budesonide proved suitable alternative as an internal standard. Conclusion: Since docetaxel and celecoxib could be co-administered for the treatment of a wide range of cancers such as non-small cell lung carcinoma, the developed method is particularly advantageous for routine therapeutic drug monitoring and pharmacokinetic studies of these drugs.

Background Delirium is a neurobehavioral syndrome, which is characterized by a fluctuation of mental status, disorientation, confusion and inappropriate behavior, and it is prevalent among hospitalized patients. Recognizing modifiable risk factors of delirium is the key point for improving our preventive strategies and restraining its devastating consequences. This study aimed to identify and investigate various factors predisposing hospitalized patients to develop delirium, focusing mostly on underlying diseases and medications. Method In a prospective, observational trial, we investigated 220 patients who had been admitted to the internal, emergency, surgery and hematology-oncology departments. We employed the Confusion Assessment Method (CAM) questionnaire, The Richmond Agitation Sedation Scale (RASS), the General Practitioner Assessment of Cognition (GPCOG), demographic questionnaire, patient interviews and medical records. Multivariate logistic regression models were used to analyze the predictive value of medications and underlying diseases for daily transition to delirium.; demographics were analyzed using univariate analysis to identify those independently associated with delirium. Results Two hundred twenty patients were enrolled; the emergency department had the most incident delirium (31.3%), and the surgery section had the least (2.4%); delirium was significantly correlated with older ages and sleep disturbance. Among multiple underlying diseases and the medications evaluated in this study, we found that a history of dementia, neurological diseases and malignancies increases the odds of transition to delirium and the use of anticoagulants decreases the incident delirium. Conclusion Approximately 1 out of 10 overall patients developed delirium; It is important to evaluate underlying diseases and medications more thoroughly in hospitalized patients to assess the risk of delirium.

Background: using a combination of chemotherapeutic agents with novel drug delivery platforms to enhance the anticancer efficacy of the drug and minimizing the side effects, is very imperative for lung cancer treatments. Objective: The aim of the present study was to develop, characterize, and optimize porous poly (D, L-lactic-co-glycolic acid) (PLGA) microparticles for simultaneous delivery of docetaxel (DTX) and celecoxib (CXB) through the pulmonary route for lung cancer. Methods: Drug-loaded porous microparticles were prepared by an emulsion solvent evaporation method. The impact of various processing and formulation variables including PLGA amount, dichloromethane volume, homogenization speed, polyvinyl alcohol volume and concentration were assessed on entrapment efficiency, mean release time, particle size, mass median aerodynamic diameter, fine particle fraction and geometric standard deviation using a two-level factorial design. An optimized formulation was prepared and evaluated in terms of size and morphology using a scanning electron microscope. Results: FTIR, DSC, and XRD analysis confirmed drug entrapment and revealed no drug-polymer chemical interaction. Cytotoxicity of DTX along with CXB against A549 cells was significantly enhanced compared to DTX and CXB alone and the combination of DTX and CXB showed the greatest synergistic effect at a 1/500 ratio. Conclusion: In conclusion, the results of the present study suggest that encapsulation of DTX and CXB in porous PLGA microspheres with desirable features are feasible and their pulmonary co-administration would be a promising strategy for the effective and less toxic treatment of various lung cancers.

Background: Delirium is a neurobehavioral syndrome, which is characterized by fluctuation of mental status, disorientation, confusion and inappropriate behavior and it is prevalent among hospitalized patients. Recognizing modifiable risk factors of delirium is the key point for improving our preventive strategies and restraining its devastating consequences. The present study investigated a wide range of possible predisposing factors of delirium, mainly focused on underlying diseases and mediations, of hospitalized patients in the different wards of a general hospital.Method: In a prospective, observational trial, we investigated 220 patients who had been admitted to the internal, emergency, surgery and hematology-oncology departments. We employed the Confusion Assessment Method (CAM) questionnaire, The Richmond Agitation Sedation Scale (RASS), the General Practitioner Assessment of Cognition (GPCOG), demographic questionnaire, patient interviews and medical records. Multivariate logistic regression models were used to analyze predictive value of medications and underlying diseases for daily transition to delirium.; demographics were analyzed using univariate analysis to identify those independently associated with delirium.Results: 220 patients were enrolled; the emergency department had the most incident delirium (%31.3) and the surgery section had the least (%2.4); delirium was significantly correlated with older ages and sleep disturbance. Among multiple underlying diseases and the medications evaluated in this study, we found that history of dementia, neurological diseases and malignancies increase the odds of transition to delirium and the use of anticoagulants decreases the incident delirium.Conclusion: Approximately, 1 out of 10 overall patients developed delirium; Considering underlying diseases and the medications as the predisposing factors of delirium would help to better predict those at risk.