Hydrotropic Solubilization of Paclitaxel: Analysis of Chemical Structures for Hydrotropic Property
AbstractPurpose. To identify hydrotropic agents that can increase aqueous paclitaxel (PTX) solubility and to study the chemical structures necessary for hydrotropic properties so that polymeric hydrotropic agents can be synthesized.
Methods. More than 60 candidate hydrotropic agents (or hydro- tropes) were tested for their ability to increase the aqueous PTX solubility. A number of nicotinamide analogues were synthesized based on the observation that nicotinamide showed a favorable hydrotropic property. The identified hydrotropes for PTX were used to examine the structure-activity relationship. N,N-Diethylnicotinamide (NNDENA) was found to be the most effective hydrotropic agent for PTX. The aqueous PTX solubility was 39 mg/ml and 512 mg/ml at NNDENA concentrations of 3.5 M and 5.95 M, respectively. These values are 5-6 orders of magnitude greater than the intrinsic solubility of 0.30 ± 0.02 μg/ml. N-Picolylnicotinamide, N-allylnicotinamide, and sodium salicylate were also excellent hydrotropes for PTX. Solubility data showed that an effective hydrotropic agent should be highly water soluble while maintaining a hydrophobic segment.
 The present study identified several hydrotropic agents effective for increasing aqueous solubility of PTX and analyzed the structural requirements for this hydrotropic property. This information can be used to find other hydrotropic compounds and to synthesize polymeric hydrotropes that are effective for PTX and other poorly water-soluble drugs.

title: Buccal permeation of [D-Ala(2), D-Leu(5)]enkephalin from liquid crystalline phases of glyceryl monooleate.
abstract: The ex vivo buccal permeability of a [D-Ala(2), D-Leu(5)]enkephalin (DADLE) and glyceryl monooleate (GMO) was examined from the cubic and lamellar liquid crystalline phases of GMO and aqueous phosphate-buffered saline (pH 7.4, PBS) solution across excised porcine buccal mucosa mounted in a Franz cell. GMO was released in vitro from the liquid crystalline phases indicating the erosion of the liquid crystal matrices. GMO released from the liquid crystalline matrices permeated the porcine buccal mucosa with fluxes of 0.10+/-0.03 and 0.07+/-0.00%/cm(2) per h for the cubic and lamellar phases, respectively. The flux of DADLE (1.21+/-0.32 and 1. 15+/-0.11%/cm(2) per h for the cubic and lamellar phases, respectively) from the liquid crystalline phases was significantly enhanced by the GMO compared with PBS solution (0.43+/-0.08%/cm(2) per h) during the initial permeation phase (t<3 h). Our results suggest that the cubic and lamellar liquid crystalline phases can be considered as promising buccal drug carriers for peptide drugs as well as acting as permeation enhancers.

title: Enhancedex vivo buccal transport of propranolol: Evaluation of phospholipids as permeation enhancers
abstract: The aim of the present study was to evaluate the effects of two phospholipid permeation enhancers, lysophosphatidylcholine (LPC) and didecanoylphosphatidylcholine (DDPC), along with a fusidic acid derivative, sodium taurodihydrofusidate (STDHF) and ethanol (EtOH) on the buccal transport of propranolol hydrochloride (PPL) using anex vivo buccal diffusion model. The permeation rate of [3H]PPL as measured by steady-state fluxes increased with increasing EtOH concentration. A significant flux enhancement (P<0.05) was achieved by EtOH at 20 and 30 %v/v concentrations. At a 0.5 %w/v permeation enhancer concentration, the buccal permeation of [3H]PPL was significantly enhanced by all the enhancers studied (i.e., LPC, DDPC and STDHF) compared to the control (phosphate-buffered saline pH 7.4, PBS). LPC and DDPC displayed a greater degree of permeation enhancement compared with STDHF and EtOH-PBS mixtures with an enhancement ratio of 3.2 and 2.9 for LPC and DDPC, respectively compared with 2.0 and 1.5 for STDHF and EtOH:PBS 30:70 %v/v mixture, respectively. There was no significant difference between LPC and DDPC for the flux values and apparent permeability coefficients of [3H]PPL. These results suggest that phospholipids are suitable as permeation enhancers for the buccal delivery of drugs.

title: The effect of storage conditions on the permeability of porcine buccal mucosa
abstract: The impact of storage conditions on the permeability of porcine buccal mucosa to [3H]water and [14C]mannitol was assessed. The fresh porcine buccal tissue (fresh tissue) was obtained by utilizing pig heads within 24 hours of slaughter. The stored and frozen porcine buccal tissues (stored tissue and frozen tissue) were obtained after the storage of the tissue intact in the pig heads at 4 degrees C or -20 degrees C, respectively, for 24 h. The results demonstrated that the barrier properties of the porcine buccal mucosa were maintained with regard to [3H]water permeability when stored at 4 degrees C for 24 h. However, freezing the tissue resulted in tissue damage illustrated by a significant increase in [3H]water permeability. [14C]Mannitol does not appear to be a suitable model solute to assess the ex vivo permeability of porcine buccal mucosa due to its extremely low permeability.

title: Rational design, synthesis, and biological evaluation of progesterone-modified MRI contrast agents.
abstract: A series of contrast agents for magnetic resonance imaging (MRI) aimed at noninvasively determining the hormone receptor status of cancer in vitro was developed. These MRI contrast agents were prepared by conjugating progesterone to clinically used Gd(III) chelates. These agents exhibited higher progesterone receptor binding affinities in the nanomolar range and intracellular accumulation. High logP values of the modified compounds suggested that the lipophilicity of the steroid conjugates may have contributed to membrane permeability. Synchrotron radiation X-ray fluorescence microscopy and magnetic resonance images revealed that the synthesized conjugates showed the greatest cellular accumulation and significant increase in relaxivity in vitro compared to the previously developed steroid-modified agent. Transcriptional assays using the progesterone response element linked to luciferase indicated that the contrast agents entered the cell, interacted with the biological target, and drove specific progesterone-mediated transcription.

title: Factor structure investigation of perceived facilitators and barriers in end-of-life care among Korean nurses.
abstract: The aim of this study was to assess the validity and reliability of the Korean version of a questionnaire assessing facilitators/barriers in end-of-life care that was originally developed for nurses in the USA.



Back-translation was undertaken to produce the Korean version. A principal component analysis with varimax rotation and Cronbach's alpha was used to test factorial validity and reliability, respectively.



The analysis examined data from 383 nurses in a tertiary hospital in Korea. For end-of-life care facilitators, five factors accounted for 59% of the total variance. The factors were labeled "family preparedness", "support for nurses", "nurse-patient relationship", "transition after death", and "decision-making". Six factors, explaining 59% of the variance, were extracted for end-of-life care barriers. These factors were "misunderstanding patient's will", "preoccupied nursing workload", "lack of institutional support", "dealing with family's maladaptive coping", "visiting hours", and "communication about patient's status with family members". Cronbach's alpha was 0.89 for the 23 facilitator items and 0.90 for the 24 barrier items.



Overall, the findings demonstrate that the questionnaire has measurement properties in a sample of Korean nurses. Further studies are needed with different populations to reflect end-of-life care in various clinical settings.

title: Electrical and thermal coupling to a single-wall carbon nanotube device using an electrothermal nanoprobe.
abstract: We utilize a multifunctional atomic force microscope (AFM) cantilever applying highly localized temperature and electric fields to interrogate transport in single-wall carbon nanotube field-effect transistors (CNTFETs). The probe can be operated either in contact with the CNT, in intermittent contact, or as a Kelvin probe, and can independently control the electric field, mechanical force, and temperature applied to the CNT. We modulate current flow in the CNT with tip-applied electric field, and find this field-effect depends upon both cantilever heating and CNT self-heating. CNT transport is also investigated with AFM tip temperature up to 1170 degrees C. Tip-CNT thermal resistance is estimated at 1.6 x 10(7) K/W and decreases with increasing temperature. Threshold force (<100 nN) for reliable contact mode imaging is extracted and used to determine set points for nanotube manipulation, such as displacement or cutting. The ability to measure thermal coupling to a single-molecule electronic device could offer new insights into nanoelectronic devices.

title: Bioconjugated Ag nanoparticles and CdTe nanowires: metamaterials with field-enhanced light absorption.
abstract: The hybrid assembly of inorganic and metallic nanomaterials by means of chemical and biological bonding to yield manifold optical and electromagnetic properties has received widespread attention. Currently available highly monodispersed nanomaterials such as semiconductors and noble metals that can be conjugated by ligand–receptor, antigen– antibody reactions, polymer tethering, and DNA hybridization are used as building blocks for 2D or 3D superstructures in which new collective properties of these artificial assemblies have been obtained. They represent a large class of newmaterials (i.e., metamaterials) in which the properties are determined not only by classical atomic composition, but also by nanoscale organization of structural components. Recently, metamaterials based on metallic composites have received special attention as these are expected to display negative values for permittivity and refractive index. This property should lead to a multitude of unique optical effects. Many of these effects are related to surface plasmons on Au or Ag nanoparticles (NPs), which generate exceptionally high localized electromagnetic fields, and have been exploited in surface-enhanced Raman spectroscopy and some optoelectronic devices. 22] Metamaterials from semiconductors and their combinations with metals can also produce optical effects that are useful for development of advanced sensing and imaging technologies. Recently, we

title: A Novel Quantitative Measure of Breast Curvature Based on Catenary
abstract: Quantitative, objective measurements of breast curvature computed from clinical photographs could be used to investigate factors that impact reconstruction and facilitate surgical planning. This paper introduces a novel quantitative measure of breast curvature based on catenary. A catenary curve is used to approximate the overall curvature of the breast contour, and the curvature measure is extracted from the catenary curve. The catenary curve was verified by comparing its length, the area enclosed by the curve, and the curvature measure from the catenary curve to those from manual tracings of the breast contour. The evaluation of the proposed analysis employed untreated and postoperative clinical photographs of women who were undergoing tissue expander/implant (TE/Implant) reconstruction. Logistic regression models were developed to distinguish between the curvature of breasts undergoing TE/Implant reconstruction and that of untreated breasts based on the curvature measure and patient variables (age and body mass index). The relationships between the curvature measures of untreated breasts and patient variables were also investigated. The catenary curve approximates breast curvature reliably. The curvature measure contains useful information for quantifying the curvature differences between breasts undergoing TE/Implant reconstruction and untreated breasts, and identifying the effect of patient variables on the breast shape.