Effect of nonionic surfactants in release media on accelerated in-vitro release profile of sirolimus eluting stents with biodegradable polymeric coating

It is a well-known fact that sirolimus (SRL) undergoes degradation process via hydrolysis in aqueous media, leading to incorrect assessment of drug amount and thus release characteristics of formulations. The main objective of the present study was to evaluate the effect of nonionic surfactants in media on in-vitro release profiles for sirolimus eluting stents (SES) coated with biodegradable polymeric matrix. Phosphate buffer and acetate buffer incorporating nonionic surfactants with varying concentrations were examined for adequate solubility and stability (by RP-HPLC). Good sink condition was achieved in phosphate buffer (at pH 4.0) with 1.0% Tween 20, 1.0% Brij 35% and 0.5% Brij 58. Hydrodynamic size (by DLS) and the micelle-water partition coefficient (P) with standard free energy of solubilization (∆Gs°) of drug were evaluated to get some understanding about the solubilization phenomena. About 80% of drug release during the period of 48 h was achieved in optimized drug release media which was 1.0% Tween 20 in phosphate buffer pH 4.0. The obtained accelerated SRL release profile in optimized medium correlated well with the real time in-vitro release in phosphate buffer (pH 7.4). Surface morphology changes (by SEM), changes in gravimetric weights and molecular weight change (by GPC) were examined before and after drug release to understand the drug release mechanism which explains that the polymer did not undergo degradation during the drug release

Nanoparticles eluting stents for coronary intervention: Formulation, characterization and in vitro evaluation

Coronary artery disease (CAD) is currently a leading cause of death worldwide. In the history of percutaneous coronary intervention for the treatment of CAD, a drug-eluting stent (DES) is recognized as a revolutionary technology that has the unique ability to significantly reduce restenosis and provide both mechanical and biological solutions simultaneously to the target lesion. The aim of the research work was to design and fabricate DES coated with a nanoparticulate drug formulation. Sirolimus, an inhibitor of the smooth muscle cell (SMC) proliferation and migration, was encapsulated in polymeric nanoparticles. The nanoparticle formulation was characterized for various physicochemical parameters. Cell viability and cell uptake studies were performed using human coronary artery smooth muscle cells (HCASMCs). The developed nanoparticle formulation showed enhanced efficacy compared to plain drug solution and exhibited time-dependent uptake into the HCASMCs. The developed nanoparticle formulation was coated on the FlexinniumTM ultra-thin cobalt-chromium alloy coronary stent platform. The nanoparticle coated stents were characterized for morphology and residual solvent analysis. In-vitro drug release was also evaluated. Ex-vivo arterial permeation was carried out to evaluate the nanoparticle uptake from the surface of the stents. The characterization studies together corroborated that the developed nanoparticle coated stent can be a promising replacement of the current drug-eluting stents.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Molecular survey of basidiomycetes and divergence time estimation: An Indian perspective

<div><p>This study outlines the biodiversity of mushrooms of India. It reveals the molecular biodiversity and divergence time estimation of basidiomycetes from Gujarat, India. A total of 267 mushrooms were collected from 10 locations across the state. 225 ITS sequences were generated belonging to 105 species, 59 genera and 29 families. Phylogenetic analysis of Agaricaceae reveals monophyletic clade of <i>Podaxis</i> differentiating it from <i>Coprinus</i>. Further, the ancient nature of <i>Podaxis</i> supports the hypothesis that gasteroid forms evolved from secotioid forms. Members of Polyporaceae appeared polyphyletic. Further, our results of a close phylogenetic relationship between <i>Trametes</i> and <i>Lenzites</i>lead us to propose that the genera <i>Trametes</i> may by enlarged to include <i>Lenzites</i>. The tricholomatoid clade shows a clear demarcation for Entolomataceae. However, Lyophyllaceae and Tricholomataceae could not be distinguished clearly. Distribution studies of the mushrooms showed omnipresence of <i>Ganoderma</i> and <i>Schizophyllum</i>. Further, divergence time estimation shows that Dacrymycetes evolved in the Neoproterozoic Era and Hymenochaetales diverged from Agaricomycetes during the Silurian period.</p></div

UPGMA phylogeny (ITS) of the Tricholomatoid clade–Phylogenetic tree showing relationships of different species belonging to a Tricholomatoid clade (Clade including Entolomataceae, Tricholomataceae and Lyophyllaceae families).

<p>Bootstrap values > 50 are shown at the branches.</p

Molecular survey of basidiomycetes and divergence time estimation: An Indian perspective - Fig 9

<p><b>Barcode gap analysis–scatterplots showing overlapping of (a) max Intra-specific vs nearest neighbor (b) mean Intra-specific vs nearest neighbor; histogram plots showing distribution of (c) mean Intra-specific distances for each species and (d) frequency histogram of distance to nearest neighbor</b>.</p

Molecular survey of basidiomycetes and divergence time estimation: An Indian perspective - Fig 2

<p><b>ITS phylogeny of the Agaricaceae family inferred by UPGMA analysis—</b>Numbers at internodes refer to confidence estimates based on 100 bootstraps (only those > 50 are given).</p

Sampling sites of Gujarat used in this study.

<p>Sampling sites of Gujarat used in this study.</p

Molecular survey of basidiomycetes and divergence time estimation: An Indian perspective - Fig 8

<p><b>Phylogenetic trees generated by UPGMA analysis from the ITS barcode sequences for (a) Fomitopsidaceae and (b) Meruliaceae</b>.</p