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We aimed to characterize the population pharmacokinetics (PK) of vedolizumab for acute graft‐versus‐host disease prophylaxis in adults undergoing allogeneic hematopoietic stem cell transplantation (allo‐HSCT) and assess potential clinically relevant covariates. Dosing, patient characteristics, and PK from a phase 1b, open‐label, dose‐finding study of vedolizumab 75 mg initial dose escalated to 300 mg and a phase 3 study of vedolizumab 300 mg in patients receiving allo‐HSCT were analyzed using a two‐compartment population PK model with linear elimination. Covariates included age, race, weight, sex, albumin, lymphocyte count, GvHD type, and concomitant medications. Weight, albumin, and lymphocyte count were time‐varying covariates. Model selection was driven by goodness‐of‐fit criteria, precision of parameter estimates, and visual predictive checks. In 193 patients undergoing allo‐HSCT, vedolizumab PK were well described by a two‐compartment, linear PK model. Using reference covariate values, final parameter estimates (95% confidence intervals [CI]) were: clearance, 0.148 (0.136, 0.162) L/day; central volume of distribution, 3.12 (3.03, 3.21) L; intercompartmental clearance, 0.500 (0.408, 0.612) L/day; and peripheral volume of distribution, 3.95 (3.52, 4.44) L. Weight and albumin were the most important predictors of vedolizumab PK, with clearance decreasing by ≈20% for low body weight/high albumin and increasing by ≈30% for high body weight/low albumin. There was an inverse relationship between vedolizumab clearance and age, but no detectable effect for lymphocyte count or GvHD type. Post hoc analyses did not detect any relationship between vedolizumab PK and concomitant medications. In summary, the covariates studied did not have a clinically meaningful effect on the PK of vedolizumab. [ABSTRACT FROM AUTHOR]

Nanoparticle technology has made an essential contribution to the pharmaceutical industry and has received considerable attention in comparison with the other domains. In the present study, ionic gelation via a novel combined system of nebulizer and falling film (IG‐NFF) has been proposed. The purpose of the design of this system is to increase the contact surface between the chitosan and sodium tripolyphosphate (STPP) for the preparation of monodisperse and spherical chitosan nanoparticles, because in both nebulizer and falling film systems, the surface‐to‐volume ratio of liquid increases. The formation of these nanoparticles is based on ionic interactions between the negatively charged phosphate groups in the STPP and positively charged amine groups on the chitosan. In this research, the effects of chitosan concentration, STPP concentration, the distance of the nebulizer from the inclined plate, gas to liquid flow rate ratio, and the initial chitosan solution pH on the z‐average size, polydispersity index (PDI), and morphology of nanoparticles formed by IG‐NFF were studied. The results showed that the IG‐NFF process has the ability to produce spherical particles with highly uniform sizes. The mean size of obtained chitosan nanoparticles was in the range of 80–320 nm, and the PDI value ranged from 0.08–0.30. [ABSTRACT FROM AUTHOR]

Background and purpose: In recent years, the interest in chitosan nanoparticles has increased due to their application, especially in drug delivery. The main aim of this work was to find a suitable method for simulating pharmaceutical nanoparticles with computational fluid dynamics (CFD) modeling and use it for understanding the process of nanoparticle formation in different types of microchannels. Experimental approach: Active and passive microchannels were compared to find the advantages and disadvantages of each system. Twenty-eight experiments were done on microchannels to quantify the effect of 4 parameters and their interactions on the size and polydispersity index (PDI) of nanoparticles. CFD was implemented by coupling reactive kinetics and the population balance method to simulate the synthesis of chitosan/tripolyphosphate nanoparticles in the microchannel. Findings/Results: The passive microchannel had the best performance for nanoparticle production. The most uniform microspheres and the narrowest standard deviation (124.3 nm, PDI = 0.112) were achieved using passive microchannel. Compared to the active microchannel, the size and PDI of the nanoparticles were 28.7% and 70.5% higher for active microchannels, and 55.43% and 105.3% higher for simple microchannels, respectively. Experimental results confirmed the validity of CFD modeling. The growth and nucleation rates were determined using the reaction equation of chitosan and tripolyphosphate. Conclusion and implications: CFD modeling by the proposed method can play an important role in the prediction of the size and PDI of chitosan/tripolyphosphate nanoparticles in the same condition and provide a new perspective for studying the production of nanoparticles by numerical methods. [ABSTRACT FROM AUTHOR]

Background: A correlation is suggested between oral lichen planus (OLP) and the human papillomavirus (HPV) with possible malignant transformation potential in OLP. Objectives: The present study aimed at evaluating the prevalence of HPV-16 and HPV-18 as the most recognized oncogenic subtypes and relatively recently introduced subtype HPV33 in OLP samples. Methods: This retrospective study was carried out on 32 OLP samples (consisting of 12 reticular and 20 erosive forms) and 20 healthy oral mucosa samples. Polymerase chain reaction (PCR) was undertaken to identify HPV Deoxyribonucleic Acid (DNA). Subsequently, the samples positive for HPV DNA underwent PCR analysis again with the specific primers. The data were analyzed statistically by Fisher's exact test regarding the significance level of lower than 0.05. Results: Eight out of 32 OLP samples (25%) and none of the 20 normal mucosa samples (0%) exhibited HPV DNA. The presence of HPV in the OLP group was significantly higher than that in the normal mucosa (P = 0.014). Also, all the samples that exhibited HPV DNA were registered as the erosive form. Besides, one sample (3.12%) exhibited the 873-bp band, which was attributed to HPV-18, and 7 samples (21.87%) exhibited the 300-bp band, which was attributed to HPV-33. Conclusions: Based on the recent findings in the current study of the Iranian population, the presence of high-risk HPV subtypes, whether primarily or as a secondary infection, can suggest the malignant transformation potential for the studied OLP samples. The exclusive presence of these subtypes in the erosive type of this lesion and the noticeable presence of HPV-33 might reflect this issue's importance. However, further studies are necessary to evaluate the possibility of a higher proliferation rate of HPV in erosive lichen planus and identify its possible malignant transformation mechanism. [ABSTRACT FROM AUTHOR]

This study, for the first time, tries to provide a simultaneous experimental and computational fluid dynamic (CFD) simulation investigation for production of uniform, reproducible, and stable polylactic-co-glycolic acid (PLGA) nanoparticles. CFD simulation was carried out to observe fluid flow behavior and micromixing in microfluidic system and improve our understanding about the governing fluid profile. The major objective of such effort was to provide a carrier for controlled and sustained release profile of different drugs. Different experimental parameters were optimized to obtain PLGA nanoparticles with proper size and minimized polydispersity index. The particle size, polydispersity, morphology, and stability of nanoparticles were compared. Microfluidic system provided a platform to control over the characteristics of nanoparticles. Using microfluidic system, the obtained particles were more uniform and harmonious in size, more stable, monodisperse and spherical, while particles produced by batch method were non-spherical and polydisperse. The best size and polydispersity index in the microfluidic method was obtained using 2% PLGA and 0.0625% (w/v) polyvinyl alcohol (PVA) solutions, and the flow rate ratio of 10:0.6 for PVA and PLGA solutions. CFD simulation demonstrated the high mixing intensity of about 0.99 at optimum condition in the microfluidic system, which is the possible reason for advantageous performance of this system. Altogether, the results of microfluidic-assisted method were found to be more reproducible, predictable, and controllable than batch method for producing a nanoformulation for delivery of drugs. [ABSTRACT FROM AUTHOR]