Mutant p53 accumulation has been shown to induce multidrug resistance (MDR1) gene and ATP binding cassettes (ABCs)-based drug efflux in human breast cancer cells. In the present work we have found that transcriptional activation of the oxidative stress-responsive heat shock factor 1 (HSF-1) and expression of heat shock proteins, including Hsp27 which is normally known to augment proteosomal p53...

Selective accumulation of pH-responsive polymersomes in the synovium arthritic joints empower target delivery drug molecules within macrophages and synoviocytes. Hence, bestow complete shut-down synovial inflammation hinder arthritis progression. This is reported by Giuseppe Battaglia co-workers article number 2100167

Calliphora vicina larvae were fed on drug-laden muscle from three suicides involving amitriptyline, temazepam and a combination of trazodone and trimipramine; triplicate daily harvestings were analysed. The limit of detection for all four drugs was 0.01 micrograms drug/g larvae. Mean drug concentrations (microgram/g) in the initial muscle were:amitriptyline, 2.68; temazepam, 4.04; trazodone, 21...

Recently, the European Medicines Agency (EMA) published the new draft guideline on the pharmacokinetic and clinical evaluation of modified release (MR) formulations. The draft guideline contains the new requirement of performing multiple dose (MD) bioequivalence studies, in the case when the MR formulation is expected to show 'relevant' drug accumulation at steady state (SS). This new requireme...

In order to study the mechanism of etoposide (VP-16) resistance in human tumor cells and to assess the role of P-170 glycoprotein in VP-16 accumulation, we have examined the uptake and efflux of VP-16 in both sensitive and multidrug-resistant MCF-7 human breast and HL60 human promyelocytic leukemia cells. The drug-resistant cells, MCF-7/ADR and HL60/ADR, were selected for resistance to adriamyc...

Renal transporter-mediated drug-drug interactions (DDIs) are of significant clinical concern, as they can adversely impact drug disposition, efficacy, and toxicity. Emerging evidence suggests that human renal organic cation transporter 2 (hOCT2) and multidrug and toxin extrusion proteins 1 and 2-K (hMATE1/2-K) exhibit substrate-dependent inhibition, but their impact on renal drug secretion and ...

Although the shortcomings of small molecular antitumor drugs were efficiently improved by being entrapped into nanosized vehicles, premature drug release and insufficient tumor targeting demand innovative approaches that boost the stability and tumor responsiveness of drug-loaded nanocarriers. Here, we show the use of the core cross-linking method to generate a micelle with enhanced drug encaps...

Four multidrug-resistant variants of the human squamous lung cancer cell line SW-1573 with levels of doxorubicin resistance ranging from 10- to 2000-fold were characterized with respect to drug accumulation and efflux, subcellular drug distribution pattern, antioxidant defenses, and P-glycoprotein expression. For all these parameters except the antioxidant defenses a correlation was observed wi...

Objectives : Drug induced-phospholipidosis is a pathological state caused by repeated administration of cationic amphiphilic drugs. The mechanism of drug-induced phospholipidosis is unclear. Several hypotheses have been proposed, such as inhibition of phospholipase, upregulated phospholipid synthesis, increased uptake of phospholipids, and inhibition of intracellular phospholipid traffic. Among...

Drug delivery systems could potentially overcome low bioavailability and gastrointestinal toxicity, which are the major challenges for the development of oral anticancer drugs. Herein, we demonstrate the ability of styrene maleic acid (SMA) nanomicelles encapsulating epirubicin to traverse in vitro and ex vivo models of the intestinal epithelium without affecting the tissue integrity. Further, ...