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In vivo pharmacokinetic studies and intracellular delivery of methotrexate by means of glycine-tethered PLGA-based polymeric micelles

Publication date: 15 March 2017 Source:International Journal of Pharmaceutics, Volume 519, Issues 1–2 Author(s): Madhwi, Rajendra Kumar, Pramod Kumar, Bhupinder Singh, Gajanand Sharma, Om Prakash Katare, Kaisar Raza Methotrexate (MTX) is a widely used drug for the management of various kinds of cancers. However, numerous challenges are associated with MTX like poor aqueous solubility, dose-dependent side effects and poor-bioavailability. With an aim to explore the potential benefits in drug delivery of MTX, it was intended to fabricate glycine-PLGA-based polymeric micelles. Glycine was chemically linked to PLGA and the linkage was confirmed by FT-IR, and NMR-Spectroscopy. The developed polymeric micelles offered substantial loading to MTX with a pH-dependent drug release profile. The drug was released maximally at the cancer cell pH vis-à-vis blood plasma pH. The cytotoxicity of drug against MDA-MB-231 cell lines was enhanced by approx. 100% and the confocal laser scanning microscopy confirmed the localization of dye-tagged nanocarriers in the interiors of cancer cells. The bioavailable fraction of the drug was increased by approx. 4-folds, whereas elimination half-life was enhanced by around two-folds in Wistar rats. The novel approach offers a biodegradable and promising carrier for the better delivery of anticancer agents with immense promises of efficacy enhancement, improved delivery and better pharmacokinetic profile. Graphical abstract
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research

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This study included all patients with non-metastatic primary T1 UBC reported to the Swedish National Register of Urinary Bladder Cancer (SNRUBC) from 1997 to 2014, excluding those treated with primary cystectomy. Differences between groups were evaluated using chi-squared tests and logistic regression, and survival was investigated using Kaplan-Meier and log-rank tests and Cox proportional hazards analysis. RESULTS: In all, 7681 patients with T1 UBC (77% male, 23% female) were included. Females were older than males at the time of diagnosis (median age at presentation 76 and 74 years, respectively; p 
Source: Scandinavian Journal of Urology - Category: Urology & Nephrology Tags: Scand J Urol Source Type: research
Conclusion For the first time the Bayesian estimates of IRs and the yearly expected numbers of cases for each rare cancer in each individual European country were calculated. Moreover, the indicator T is useful to convey incidence estimates for exceptionally rare cancers and in small countries; it far exceeds the professional lifespan of a medical doctor.
Source: Cancer Epidemiology - Category: Cancer & Oncology Source Type: research
Publication date: June 2018 Source:European Polymer Journal, Volume 103 Author(s): Mostafa Zamani, Kobra Rostamizadeh, Hamidreza Kheiri Manjili, Hossein Danafar Amphiphilic FA-L-PEG-PCL (PEG: Poly ethylene glycol-hydrophilic segment, FA: Folic acid-targeting agent, L: Lysine-linker, PCL: Poly caprolactone-hydrophobic segment) copolymer was synthesized. Proton nuclear magnetic resonance (HNMR), Fourier-transform infrared spectroscopy (FT-IR), Dynamic light scattering (DLS), atomic force microscopy (AFM), dynamic scanning colorimetry (DSC) were used for characterization of synthesizes copolymers. For determining cytotoxicit...
Source: European Polymer Journal - Category: Chemistry Source Type: research
AbstractRecent reports identify NLR (the ratio between absolute neutrophils counts, ANC, and absolute lymphocyte count, ALC), as predictor of progression-free survival (PFS) and overall survival (OS) in cancer patients. We retrospectively tested NLR and LMR (the ratio between absolute lymphocyte and monocyte counts) in newly diagnosed Hodgkin lymphoma (HL) patients treated upfront with a PET-2 risk-adapted strategy. NLR and LMR were calculated using records obtained from the complete blood count (CBC) from 180 newly diagnosed HL patients. PFS was evaluated accordingly to Kaplan-Meier method. Higher NLR was associated to ad...
Source: Annals of Hematology - Category: Hematology Source Type: research
Conclusions: TETs with clearly invasive or metastatic features seen on CT are associated with having higher AJCC/UICC pathologic TNM stage, as expected. However, features of lobulated contour and heterogeneous internal density are also associated with higher stage disease. These findings need to be validated in an independent cohort.
Source: Journal of Thoracic Imaging - Category: Radiology Tags: Original Articles Source Type: research
Initial staging of gastric cancer consists of computed tomography (CT) and gastroscopy. In locally advanced (cT3 –4) gastric cancer, fluorodeoxyglucose positron emission tomography with CT (FDG-PET/CT or PET) a...
Source: BMC Cancer - Category: Cancer & Oncology Authors: Tags: Study protocol Source Type: research
Peptides labeled with positron-emitting isotopes are emerging as a versatile class of compounds for the development of highly specific, targeted imaging agents for diagnostic imaging via positron-emission tomography (PET) and for precision medicine via theranostic applications. Despite the success of peptides labeled with gallium-68 (for imaging) or lutetium-177 (for therapy) in the clinical management of patients with neuroendocrine tumors or prostate cancer, there are significant advantages of using fluorine-18 for imaging.
Source: Nuclear Medicine and Biology - Category: Nuclear Medicine Authors: Source Type: research
This article reviews the emerging roles of functional imaging in the assessment of peritoneal carcinomatosis in ovarian cancer, focusing on the use of diffusion-weighted magnetic resonance imaging (DW-MRI) and 2-[18F]-fluoro-2-deoxy-d-glucose positron-emission tomography combined with computed tomography (PET-CT), their advantages and shortcomings as well as the added-value over conventional imaging.
Source: Clinical Radiology - Category: Radiology Authors: Tags: Pictorial Review Source Type: research
AbstractPurposeTumor delineation within an atelectasis in lung cancer patients is not always accurate. When T staging is done by integrated 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG)-positron emission tomography (PET)/X-ray computer tomography (CT), tumors of neuroendocrine differentiation and slowly growing tumors can present with reduced FDG uptake, thus aggravating an exact T staging. In order to further exhaust information derived from [18F]FDG-PET/CT, we evaluated the impact of CT density and maximum standardized uptake value (SUVmax) for the classification of different tumor subtypes within a surrounding atelectasis,...
Source: Molecular Imaging and Biology - Category: Molecular Biology Source Type: research
Conclusions: Our results confirm the predictive and prognostic value of tumor ΔSUVmax in ER-positive /HER2-negative advanced BCs patients. These findings can be helpful to select high-risk patients within trials investigating novel treatment strategies. PMID: 29662649 [PubMed]
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
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