Smart probe for simultaneous detection of copper ion, pyrophosphate, and alkaline phosphatase in vitro and in clinical samples

Wilson's disease (WD), which might lead to acute liver failure, is an inherited disorder characterized by accumulation of copper (Cu2+) in the brain, the liver, and other vital organs. In the clinic, decreased serum alkaline phosphatase (ALP) concentration is used for WD diagnosis. But to the best of our knowledge, using a fluorescent probe to simultaneously detect multiple factors in WD (e.g., Cu2+, pyrophosphate (PPi), and ALP) has not been reported. Herein, we rationally designed a fluorescent switch (E)-8-((4-methylbenzylidene)amino)napthalen-1-amine (L) and successfully applied it for sequential and selective detections of Cu2+, PPi, and ALP in vitro, in living cells and synovial fluid samples with "Off," "On," and "Off" fluorescence signals, respectively. Considering the obvious correlations among Cu2+, PPi, and ALP in WD, we envision that our fluorescent probe L could be applied to in vitro diagnosing WD in the near future

Development of 4-sulfated N-acetyl galactosamine anchored chitosan nanoparticles: a dual strategy for effective management of Leishmaniasis

The present investigation reports the modification of chitosan nanoparticles with a ligand 4-sulfated N-acetyl galactosamine (4-SO<SUB>4</SUB>GalNAc) for efficient chemotherapy in leishmaniasis (SCNPs) by using dual strategy of targeting. These (SCNPs) were loaded with amphotericin B (AmB) for specific delivery to infected macrophages. Developed AmB loaded SCNPs (AmB-SCNPs) had mean particle size of 333 ± 7 nm, and showed negative zeta potential (−13.9 ± 0.016 mV). Flow cytometric analysis revealed enhanced uptake of AmB–SCNPs in J774A.1, when compared to AmB loaded unmodified chitosan NPs (AmB–CNPs). AmB–SCNPs provide significantly higher localization of AmB in liver and spleen as compared to AmB–CNPs after i.v. administration. The study stipulates that 4-SO<SUB>4</SUB>GalNAc assures of targeting, resident macrophages. Highly significant anti-leishmanial activity (P &#60; 0.05 compared with AmB–CNPs) was observed with AmB–SCNPs, causing 75.30 ± 3.76% inhibition of splenic parasitic burdens. AmB–CNPs and plain AmB caused only 63.89 ± 3.44% and 47.56 ± 2.37% parasite inhibition, respectively, in Leishmania-infected hamsters (P &#60; 0.01 for AmB–SCNPs versus plain AmB and AmB–CNPs versus plain AmB)

Development, characterization and toxicological evaluations of phospholipids complexes of curcumin for effective drug delivery in cancer chemotherapy

<p>The purpose of this study was to prepare and characterize the complexes between curcumin (CU) phosphatidylcholine (PC) and hydrogenated soya phosphatidylcholine (HSPC) and to evaluate their anticancer activity. These CU–PC and CU–HSPC complexes (CU–PC-C and CU–HSPC-C) were evaluated for various physical parameters like Fourier transform infrared spectroscopy, melting point, solubility, scanning electron microscopy and the <i>in vitro</i> drug release study. These data confirmed the formation of phospholipids complexes. The <i>in vitro</i> hemolysis study showed that the complex was non-hemolytic. The anti-cancer potential of the complexes was demonstrated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay in MCF-7 cell line. This increase may be due to the amphiphilic nature of the complexes, which significantly enhances the water and lipid solubility of the CU. Unlike the free CU (which showed a total of only 90% drug release at the end of 8 h), complex showed around 40–60% release at the end of 8 h in dissolution studies. It showed that (when given in equimolar doses) complexes have significantly decreased the amount of CU available for absorption as compared with CU-free drug. Both CU-PC-C and CU-HSPC-C were found to be non-toxic at the dose equivalent to 2000 mg/kg of body weight of CU in the toxicity study. Acute and subacute toxicity studies confirmed the oral safety of the formulation. A series of genotoxicity studies was conducted, which revealed the non-genotoxicity potential of the developed complexes. Thus, it can be concluded that the phospholipid complexes of CU may be a promising candidate in cancer therapy.</p