Subscribe: pubmed: 0724-8741
http://eutils.ncbi.nlm.nih.gov/entrez/eutils/erss.cgi?rss_guid=0spjxyiUHQBOvRATBd1pxx6pSov-3zWkF17KLjoXhfs
Preview: pubmed: 0724-8741

pubmed: 0724-8741



NCBI: db=pubmed; Term=0724-8741



 



Notch-1 siRNA and Methotrexate towards a Multifunctional Approach in Rhematoid Arthritis Management: a Nanomedicine Approach.
Related Articles

Notch-1 siRNA and Methotrexate towards a Multifunctional Approach in Rhematoid Arthritis Management: a Nanomedicine Approach.

Pharm Res. 2018 Apr 20;35(6):123

Authors: Zhao G, Zhang H

Abstract
PURPOSE: Rheumatoid arthritis (RA) is a chronic inflammatory disease and Notch pathway plays a pivotal role in synoviocytes involved in progression of RA.
METHODS: Herein, we have designed a self-assembled polymeric micelles based on polycaprolactone-polyethylene glycol (PCL-PEG) and polyethylenimine-polyethylene glycol (PEI-PEG) was prepared and loaded with methotrexate and Notch-1 siRNA for the effective treatment of rheumatoid arthritis.
RESULTS: The MTX/siRNA-loaded polymeric micelles (siM-PM) showed appreciable cellular uptake in Raw264.7 cells which were activated with LPS and did not exhibit any toxicity to Raw264.7 and HUVEC cells. The AUC of siM-PM was 4-fold higher compared to that of free MTX while t1/2 was 6 fold for siM-PM compared to that of free drug indicating the superior pharmacokinetic parameters. Importantly, siM-PM significantly reduced the paw thickness and slowed the disease progression remarkably, indicating that siM-PM is very effective in recovering the edema in arthritic animals. Importantly, 2-fold decrease in arthritic score was observed in siM-PM treated group at the end of day 24. The data clearly reveals anti-inflammatory effect of combinational nanoparticle due to the sequence specific downregulation of Notch-1 expression in the RA clinical models.
CONCLUSIONS: Overall, nanomedicine-based delivery of MTX and siRNA could overcome the side effects of small molecules and could improve the therapeutic effect of siRNA in rheumatoid arthritis.

PMID: 29679159 [PubMed - in process]




Immediate Release 3D-Printed Tablets Produced Via Fused Deposition Modeling of a Thermo-Sensitive Drug.
Related Articles

Immediate Release 3D-Printed Tablets Produced Via Fused Deposition Modeling of a Thermo-Sensitive Drug.

Pharm Res. 2018 Apr 20;35(6):124

Authors: Kempin W, Domsta V, Grathoff G, Brecht I, Semmling B, Tillmann S, Weitschies W, Seidlitz A

Abstract
PURPOSE: Dissolution speeds of tablets printed via Fused Deposition Modeling (FDM) so far are significantly lower compared to powder or granule pressed immediate release tablets. The aim of this work was to print an actual immediate release tablet by choosing suitable polymers and printing designs, also taking into account lower processing temperatures (below 100°C) owing to the used model drug pantoprazole sodium.
METHODS: Five different pharmaceutical grade polymers polyvinylpyrrolidone (PVP K12), polyethylene glycol 6000 (PEG 6000), Kollidon® VA64, polyethylene glycol 20,000 (PEG 20,000) and poloxamer 407 were successfully hot-melt-extruded to drug loaded filaments and printed to tablets at the required low temperatures.
RESULTS: Tablets with the polymers PEG 6000 and PVP K12 and with a proportion of 10% pantoprazole sodium (w/w) demonstrated a fast drug release that was completed within 29 min or 10 min, respectively. By reducing the infill rate of PVP tablets to 50% and thereby increase the tablet porosity it was even possible to reduce the mean time for total drug release to only 3 min.
CONCLUSIONS: The knowledge acquired through this work might be very beneficial for future FDM applications in the field of immediate release tablets especially with respect to thermo-sensitive drugs.

PMID: 29679157 [PubMed - in process]




Adsorption and Leachable Contamination of Flucloxacillin, Cyclosporin and Amiodarone Following Delivery Through an Intravenous Administration Set.
Related Articles

Adsorption and Leachable Contamination of Flucloxacillin, Cyclosporin and Amiodarone Following Delivery Through an Intravenous Administration Set.

Pharm Res. 2018 Apr 19;35(6):121

Authors: Woodward Z, Brooks P, Morris-Smith B, Wallis M, Ogbourne SM

Abstract
PURPOSE: Interactions between a pharmaceutical drug and its delivery device can result in changes in drug concentration and leachable contamination. Flucloxacillin, amiodarone and cyclosporin were investigated for drug concentration changes and leachable contamination after delivery through an intravenous administration set.
METHODS: Flucloxacillin, amiodarone and cyclosporin were delivered through an intravenous administration set and the eluate analysed by HPLC-UV and HPLC-MS.
RESULTS: The average recovery of flucloxacillin was 99.7% and no leachable compounds were identified. The average recovery of cyclosporin was 96.1%, which contrasts previous findings that have reported up to 50% loss of cyclosporin. This is likely due to the use of DEHP-free administration sets in this study, as adsorption of cyclosporin is linearly related to DEHP content. The average recovery of amiodarone was 91.5%. 5-hydroxymethylfurfural was identified in the amiodarone solution following delivery through the administration set as well as the 5% glucose solution used for delivery.
CONCLUSIONS: Drug/administration set interactions may modify pharmaceuticals during delivery. In this study, only 90% of the amiodarone was delivered through a generic administration set. Given the growing use of generic administration sets in hospital settings, validation of the suitability of their use is required to ensure patient safety and expected levels of efficacy.

PMID: 29675679 [PubMed - in process]




A Pharmacometric Analysis of Patient-Reported Outcomes in Breast Cancer Patients Through Item Response Theory.
Related Articles

A Pharmacometric Analysis of Patient-Reported Outcomes in Breast Cancer Patients Through Item Response Theory.

Pharm Res. 2018 Apr 19;35(6):122

Authors: Schindler E, Friberg LE, Lum BL, Wang B, Quartino A, Li C, Girish S, Jin JY, Karlsson MO

Abstract
PURPOSE: An item response theory (IRT) pharmacometric framework is presented to characterize Functional Assessment of Cancer Therapy-Breast (FACT-B) data in locally-advanced or metastatic breast cancer patients treated with ado-trastuzumab emtansine (T-DM1) or capecitabine-plus-lapatinib.
METHODS: In the IRT model, four latent well-being variables, based on FACT-B general subscales, were used to describe the physical, social/family, emotional and functional well-being. Each breast cancer subscale item was reassigned to one of the other subscales. Longitudinal changes in FACT-B responses and covariate effects were investigated.
RESULTS: The IRT model could describe both item-level and subscale-level FACT-B data. Non-Asian patients showed better baseline social/family and functional well-being than Asian patients. Moreover, patients with Eastern Cooperative Oncology Group performance status of 0 had better baseline physical and functional well-being. Well-being was described as initially increasing or decreasing before reaching a steady-state, which varied substantially between patients and subscales. T-DM1 exposure was not related to any of the latent variables. Physical well-being worsening was identified in capecitabine-plus-lapatinib-treated patients, whereas T-DM1-treated patients typically stayed stable.
CONCLUSION: The developed framework provides a thorough description of FACT-B longitudinal data. It acknowledges the multi-dimensional nature of the questionnaire and allows covariate and exposure effects to be evaluated on responses.

PMID: 29675616 [PubMed - in process]