Tightness of slip-linked polymer chains

We study the interplay between entropy and topological constraints for a polymer chain in which sliding rings (slip-links) enforce pair contacts between monomers. These slip-links divide a closed ring polymer into a number of sub-loops which can exchange length between each other. In the ideal chain limit, we find the joint probability density function for the sizes of segments within such a slip-linked polymer chain (paraknot). A particular segment is tight (small in size) or loose (of the order of the overall size of the paraknot) depending on both the number of slip-links it incorporates and its competition with other segments. When self-avoiding interactions are included, scaling arguments can be used to predict the statistics of segment sizes for certain paraknot configurations.Comment: 10 pages, 6 figures, REVTeX

Delivery modulation in silica mesoporous supports via alkyl chain pore outlet decoration

This article focuses on the study of the release rate in a family of modified silica mesoporous supports. A collection of solids containing ethyl, butyl, hexyl, octyl, decyl, octadecyl, docosyl, and triacontyl groups anchored on the pore outlets of mesoporous MCM-41 has been prepared and characterized. Controlled release from pore voids has been studied through the delivery of the dye complex tris(2,2¿-bipyridyl)ruthenium(II). Delivery rates were found to be dependent on the alkyl chain length anchored on the pore outlets of the mesoporous scaffolding. Moreover, release rates follow a Higuchi diffusion model, and Higuchi constants for the different hybrid solids have been calculated. A decrease of the Higuchi constants was observed as the alkyl chain used to tune the release profile is longer, confirming the effect that the different alkyl chains anchored into the pore mouths exerted on the delivery of the cargo. Furthermore, to better understand the relation between pore outlets decoration and release rate, studies using molecular dynamics simulations employing force-field methods have been carried out. A good agreement between the calculations and the experimental observations was observed.Financial support from the Spanish Government (projects MAT2009-14564-C04-01 and MAT2009-14564-C04-04) and the Generalitat Valencia (project PROMETEO/2009/016) is gratefully acknowledged.Aznar Gimeno, E.; Sancenón Galarza, F.; Marcos Martínez, MD.; Martínez Mañez, R.; Stroeve, P.; Cano, J.; Amoros Del Toro, P. (2012). Delivery modulation in silica mesoporous supports via alkyl chain pore outlet decoration. Langmuir. 28:2986-2996. https://doi.org/10.1021/la204438jS298629962

The use of Brazilian vegetable oils in nanoemulsions: an update on preparation and biological applications

ABSTRACT Vegetable oils present important pharmacological properties, which gained ground in the pharmaceutical field. Its encapsulation in nanoemulsions is considered a promising strategy to facilitate the applicability of these natural compounds and to potentiate the actions. These formulations offer several advantages for topical and systemic delivery of cosmetic and pharmaceutical agents including controlled droplet size, protection of the vegetable oil to photo, thermal and volatilization instability and ability to dissolve and stabilize lipophilic drugs. For these reasons, the aim of this review is to report on some characteristics, preparation methods, applications and especially analyze recent research available in the literature concerning the use of vegetable oils with therapeutic characteristics as lipid core in nanoemulsions, specially from Brazilian flora, such as babassu (Orbignya oleifera), aroeira (Schinus molle L.), andiroba (Carapa guaianiensis), casca-de-anta (Drimys brasiliensis Miers), sucupira (Pterodon emarginatus Vogel) and carqueja doce (Stenachaenium megapotamicum) oils

A biodegradable multiblock co-polymer derived from an alpha,omega-bis(methylamino)peptide and an alpha,omega-bis(oxiranylmethyl)poly(ethylene glycol)

A novel peptide containing the lysosomally degradable sequence GlyPheLeuGly and a sequence-inverting unit has been prepared. This peptide presents the methylamino groups of sarcosine (N-methylglycine) at both termini for co-polymerisation with alpha,omega-bis(oxiranylmethoxy)poly(ethylene glycol) of mean M-w 1650. Gel permeation chromatographic analysis showed the presence of a mixture of oligomers. preliminary degradation studies showed that these oligomers are cleaved by cathepsin B, an important lysosomal enzyme. (C) 2000 Elsevier Science B.V. All rights reserved

Formation of hybrid polymethylene-poly(oxyethylene) macrocycles

Maclocyclisations, particularly those forming crown ethers, normally require high dilution conditions. However, treatment of 1,9-bis(sarcosylamino)nonane with alpha,omega -bis(oxiranylmethyl) ethers derived from oligomeric poly(ethyleneglycol)s of MW 400-600 Da under high concentration conditions was found to give excellent yields of 1:1 hybrid polymethylene-poly(oxyethylene) macrocyclic crown ether derivatives. The corresponding alpha,omega -bis(oxiranylmethyl) ether derived from poly(ethyleneglycol) of mean MW 1500 Da gave polymeric material only. The macrocycles were characterised by NMR, GPC and MS. (C) 2001 Elsevier Science Ltd. All rights reserved

Midbrain and forebrain patterning delivers immunocytochemically and functionally similar populations of neuropeptide Y containing GABAergic neurons

Neurons differentiated in vitro from embryonic stem cells (ESCs) have the potential to serve both as models of disease states and in drug discovery programs. In this study, we use sonic hedgehog (SHH) and fibroblast growth factor 8 (FGF-8) to enrich for forebrain and midbrain phenotypes from mouse ESCs. We then investigate, using Ca2+ imaging and [H-3]-GABA release studies, whether the GABAergic neurons produced exhibit distinct functional phenotypes. At day 24 of differentiation, reverse transcriptase-PCR showed the presence of both forebrain (Bf-1, Hesx1, Pgc-1 alpha, Six3) and midbrain (GATA2, GATA3) selective mRNA markers in developing forebrain-enriched cultures. All markers were present in midbrain cultures except for Bf-1 and Pgc-1 alpha. Irrespective of culture conditions all GABA immunoreactive neurons were also immunoreactive to neuropeptide Y (NPY) antibodies. Forebrain and midbrain GABAergic neurons responded to ATP (1 mM). L-glutamate (30 mu M), noradrenaline (30 mu M), acetylcholine (30 mu M) and dopamine (30 mu M), with similar elevations of intracellular Ca2+([Ca2+](i)). The presence of GABA(A) and GABA(B) antagonists, bicuculline (30 mu M) and CGP55845 (1 mu M), increased the elevation of [Ca2+](i) in response to dopamine (30 mu M) in midbrain, but not forebrain GABAergic neurons. All agonists, except dopamine, elicited similar [H-3]-GABA release from forebrain and midbrain cultures. Dopamine (30 mu M) did not stimulate significant [H-3]-GABA release in midbrain cultures, although it was effective in forebrain cultures.This study shows that differentiating neurons toward a midbrain fate restricts the expression of forebrain markers. Forebrain differentiation results in the expression of forebrain and midbrain markers. All GABA(+) neurons contain NPY, and show similar agonist-induced elevations of [Ca2+](i) and [H-3]-GABA release.This study indicates that the pharmacological phenotype of these particular neurons may be independent of the addition of the patterning factors that direct neurons toward forebrain and midbrain fates. (C) 2011 Elsevier Ltd. All rights reserved

Computational Models of the Gastrointestinal Environment. 1. The Effect of Digestion on the Phase Behavior of Intestinal Fluids

Improved models of the gastrointestinal environment have great potential to assist the complex process of drug formulation. Molecular dynamics (MD) is a powerful method for investigating phase behavior at a molecular level. In this study we use multiple MD simulations to calculate phase diagrams for bile before and after digestion. In these computational models, undigested bile is represented by mixtures of palmitoyl-oleoylphosphatidylcholine (POPC), sodium glycodeoxycholate (GDX), and water. Digested bile is modeled using a 1:1 mixture of oleic acid and palmitoylphosphatidylcholine (lysophosphatidylcholine, LPC), GDX, and water. The computational phase diagrams of undigested and digested bile are compared, and we describe the typical intermolecular interactions that occur between phospholipids and bile salts. The diffusion coefficients measured from MD simulation are compared to experimental diffusion data measured by DOSY-NMR, where we observe good qualitative agreement. In an additional set of simulations, the effect of different ionization states of oleic acid on micelle formation is investigated

Molecular Structuring and Phase Transition of Lipid-Based Formulations upon Water Dispersion : A Coarse-Grained Molecular Dynamics Simulation Approach

The internal molecular structure of lipid-based formulations (LBFs) is poorly understood. In this work we aimed at establishing coarse-grained molecular dynamics simulations as a tool for rapid screening and investigation of the internal environment of these formulations. In order to study complex LBFs composed of different kinds of lipids we simulated a number of systems containing either medium-chain or long-chain lipids with varying proportions of tri-, di-, and monoglycerides. Structural and dynamic measurements and analyses identified that the internal environment in a mixture of lipids was locally ordered even in the absence of water, which might explain some of the previously reported effects on drug solubility in these systems. Further, phase changes occurring upon water dispersion are well captured with coarse-grained simulations. Based on these simulations we conclude that the coarse-grained methodology is a promising in silico approach for rapid screening of structures formed in complex formulations. More importantly it facilitates molecular understanding of interactions between excipients and water at a feasible time scale and, hence, opens up for future virtual drug formulation studies