Poly(2-oxazoline)-Based Amphiphilic Gradient Copolymers as Nanocarriers for Losartan: Insights into Drug–Polymer Interactions

The current study is focused on the development of highly stable drug nanocarriers by encapsulating losartan potassium (LSR) into an amphiphilic biocompatible poly(2-methyl-2-oxazoline)-grad-poly(2-phenyl-2-oxazoline) (PMeOxz72-grad-PPhOxz28) gradient copolymer (GC). Based on dynamic light scattering (DLS), the PMeOxz72-grad-PPhOxz28 (where the subscripts denote %wt composition of the components) GC formed micelles and aggregates of 13 nm and 96 nm in aqueous milieu. The presence of hydrophobic LSR molecules altered the structural characteristics of the GC, modulating the organization of the polymeric components and revealing the formation of hyper micellar nanostructures in addition to micelles. The 2D-NOESY experiments evidenced intermolecular interactions between the phenyl ring of LSR with the phenyl group of PPhOxz and eminent correlations between the butyl chain of LSR with the phenyl group of PPhOxz and methylene group of PMeOxz, respectively. Additionally, NMR studies as a function of temperature demonstrated that the presence of hydrophilic PMeOxz segments in the gradient core of PMeOxz72-grad-PPhOxz28 nanoassemblies induced an increased fluidity of the core matrix, especially upon heating, thus causing water penetration, resulting in increased proton mobility. Lastly, the ultrasound release profile of LSR signified that a great amount of the encapsulated LSR is tightly bound to the PMeOxz72-grad-PPhOxz28 nanoassemblies.

Further characterizations of the weak core inverse of matrices and the weak core matrix

<abstract><p>The present paper is devoted to characterizing the weak core inverse and the weak core matrix using the core-EP decomposition. Some new characterizations of the weak core inverse are presented by using its range space, null space and matrix equations. Additionally, we give several new representations and properties of the weak core inverse. Finally, we consider several equivalent conditions for a matrix to be a weak core matrix.</p></abstract>

HIFα independent mechanisms in renal carcinoma cells modulate divergent outcomes in fibronectin assembly mediated by hypoxia and CoCl2

Fibronectin (FN) is a core matrix protein that assembles to form a dynamic cellular scaffold, frequently perturbed during oncogenic transformation. Tumor hypoxia, characterized by low oxygen concentrations in the microenvironment of most solid tumors has been shown to accelerate FN assembly in fibroblasts and cancer-associated fibroblasts, cell types that produce abundant amounts of FN protein. Nevertheless, FN matrix regulation in epithelial cancer cells during hypoxia remains less well defined. In this study we investigate the assembly of the FN matrix during hypoxia in renal cancer epithelial cells, the cells of origin of renal cell carcinoma (RCC). We show that hypoxia (1% O2) specifically increases matrix disassembly and increases migratory propensity in renal cancer cells. However, HIFα stabilization using hypoxia mimetics, does not recapitulate the effect of hypoxia on FN matrix reorganization or cell migration. Using a combination of knockdown and inhibitor-based approaches, our work characterizes the signaling events that mediate these two disparate changes on the matrix and explores its functional significance on chemotactic cell migration. Our study systematically reexamines the role of hypoxia mimetics as experimental substitutes for hypoxia and provides new findings on HIFα stabilization and the FN matrix in the context of renal cancer.

In vivo Antiplasmodial Activity of Curcumin-Loaded Nanostructured Lipid Carriers

Background: It was shown that curcumin (Cur) has anti-plasmodium activity, however, its weak bioavailability, rapid metabolism, and limited chemical stability has restricted its application in clinical usages. Nanostructured lipid carriers (NLCs) are a type of drug-delivery systems (DDSs) which their core matrix is composed of both solid and liquid lipids. Objective: The aim of the current study was to prepare and characterize curcumin-loaded nanostructured lipid carriers (Cur-NLC) for malaria treatment. Methods: For the production of NLC, coconut oil and cetyl palmitate were selected as a liquid and solid lipid, respectively. In order to prepare the Cur-NLC, the microemulsion method was applied. General toxicity assay on Artemia salina and also hemocompatibility was investigated. Antimalarial activity was studied on mice infected with Plasmodium berghei. Results: The NLCs mean particle size and polydispersity index (PI) was 145 nm and 0.3, respectively. Moreover, the zeta potential of the Cur-NLC was −25 mV, as well as, the NLCs showed pseudo-spherical shape which revealed via transmission electron microscopy (TEM). The loading capacity and encapsulation efficacy of the obtained Cur-NLC were 3.1 ± 0.015% and 74 ± 3.32%, respectively. In vitro, Cur release profiles showed a sustained-release pattern up to 5 days in synthesized Cur-NLC. The results of in vivo anti-plasmodial activity against P. berghei revealed that antimalarial activity of Cur-NLC was high 2-fold compared with bare Cur at the tested dosage level. Conclusion: : The results of this study showed that NLC would be used as a potential nanocarrier for the treatment of malaria.