Formulation development of epidermal growth factor.
The information in this paper is presented to summarise various investigations in recent years to develop epidermal growth factor (EGF) delivery systems. EGF is a promising and well-characterised polypeptide that can be used in the treatment of various types of wounds and ulcers. Many approaches have been employed to deliver EGF as a stimulant for cellular activities involved in the processes of wound healing and tissue repair. Recently, emphasis is placed on the development of sustained or controlled delivery technology to optimise EGF delivery.

title: Peptide Washout and Permeability from Glyceryl Monooleate Buccal Delivery Systems
abstract: Simultaneous evaluation of the permeation and washout of a peptide from the mucoadhesive liquid crystalline phases of glyceryl monooleate (GMO) has been investigated using a donor compartment flow-through diffusion cell. [d-Ala2, d-Leu5]enkephalin (DADLE) was incorporated into the cubic and lamellar liquid crystalline phases of GMO and applied to excised porcine buccal mucosa mounted in the donor compartment flow-through cell. Phosphate-buffered saline pH 7.4 (PBS) was pumped across the upper surface of the liquid crystalline phases to mimic salivary flow. The steady-state fluxes of DADLE and GMO from the cubic phase were significantly greater than that from the lamellar phase (P<0.01). There was no statistical difference between the amounts of DADLE and GMO washed out from the lamellar and cubic phases (P>0.05). The donor compartment flow-through diffusion cell was found to be a useful tool to evaluate the impact of salivary washout on mucoadhesive oral mucosal delivery systems.

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: Hydrotropic Solubilization of Paclitaxel: Analysis of Chemical Structures for Hydrotropic Property
abstract: 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: 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: Kinetic characterization of swelling of liquid crystalline phases of glyceryl monooleate
abstract: Research in this paper focuses on the kinetic evaluation of swelling of the liquid crystalline phases of glyceryl monooleate (GMO). Swelling of the lamellar and cubic liquid crystalline phases of GMO was studied using twoIn vitro methods, a total immersion method and a Franz cell method. The swelling of the lamellar phase and GMO having 0 %w/w initial water content was temperature dependent. The swelling ratio was greater at 20°C than 37°C. The water uptake increased dramatically with decreasing initial water content of the liquid crystalline phases. The swelling rates obtained using the Franz cell method with a moist nylon membrane to mimic buccal drug delivery situation were slower than the total immersion method. The swelling was studied by employing first-order and second-order swelling kinetics. The swelling of the liquid crystalline phases of GMO could be described by second-order swelling kinetics. The initial stage of the swelling (t < 4 h) followed the square root of time relationship, indicating that this model is also suitable for describing the water uptake by the liquid crystalline matrices. These results obtained from the current study demonstrate that the swelling strongly depends on temperature, the initial water content of the liquid crystalline phases and the methodology employed for measuring the swelling of GMO.

title: Periodontal regeneration: focus on growth and differentiation factors.
abstract: Several growth and differentiation factors have shown potential as therapeutic agents to support periodontal wound healing/regeneration, although optimal dosage, release kinetics, and suitable delivery systems are still unknown. Experimental variables, including delivery systems, dose, and the common use of poorly characterized preclinical models, make it difficult to discern the genuine efficacy of each of these factors. Only a few growth and differentiation factors have reached clinical evaluation. It appears that well-defined discriminating preclinical models followed by well-designed clinical trials are needed to further investigate the true potential of these and other candidate factors. Thus, current research is focused on finding relevant growth and differentiation factors, optimal dosages, and the best approaches for delivery to develop clinically meaningful therapies in patient-centered settings.

title: Statistical intensity variation analysis for rapid volumetric imaging of capillary network flux.
abstract: We present a novel optical coherence tomography (OCT)-based technique for rapid volumetric imaging of red blood cell (RBC) flux in capillary networks. Previously we reported that OCT can capture individual RBC passage within a capillary, where the OCT intensity signal at a voxel fluctuates when an RBC passes the voxel. Based on this finding, we defined a metric of statistical intensity variation (SIV) and validated that the mean SIV is proportional to the RBC flux [RBC/s] through simulations and measurements. From rapidly scanned volume data, we used Hessian matrix analysis to vectorize a segment path of each capillary and estimate its flux from the mean of the SIVs gathered along the path. Repeating this process led to a 3D flux map of the capillary network. The present technique enabled us to trace the RBC flux changes over hundreds of capillaries with a temporal resolution of ~1 s during functional activation.

title: Estimation of anatomical locations using standard frame of reference in chest CT scans
abstract: We propose a method to establish the standard chest frame of reference (CFOR) using the rib cage in a lung CT scan. Such a reference frame is essential for referring to a certain location within a chest region and may facilitate the registration across multiple scans of a given subject as well as the comparative studies within a cohort of subjects. The robustness of the established CFOR was evaluated by estimating the anatomical locations within chest in the follow-up scan given the location in the first scan. Specifically, tracheal bifurcation point of airway tree and the center of pulmonary nodule were used as the anatomical points of interest. The CFOR was also used for exploring the spatial distribution of the anatomical location for a large number of individuals. The results show that on average the point of interest can be estimated accurately within 10.3 mm for the bifurcation point and within 12.5 mm for the pulmonary nodule’s center point. Further analyzing the spatial distribution of the CFOR coordinates across 86 subjects shows that we can localize the bifurcation point to the small subregion within the CFOR.

title: Respiration-induced B0 field fluctuation compensation in balanced SSFP: real-time approach for transition-band SSFP fMRI.
abstract: In functional MRI (fMRI) the resonance frequency shift induced from respiration is a major source of physiological noise. In transition-band SSFP fMRI the respiration-induced resonance offset not only increases noise interference, it also shifts the activation band. This leads to a reduction in the contrast-to-noise ratio (CNR) and the potential for varying contrast levels during the experiment. A novel real-time method that compensates for the respiration-induced resonance offset frequency is presented. This method utilizes free induction decay (FID) phase information to measure the resonance offset. For compensation, one can update the resonant frequency in real time by changing the transmit RF pulse and receiver phases to track the measured offset. The results show decreased signal power in the respiration frequency band and increased numbers of activated voxels with higher Z-scores compared to uncompensated experiments.

title: Protein loop modeling by using fragment assembly and analytical loop closure.
abstract: Protein loops are often involved in important biological functions such as molecular recognition, signal transduction, or enzymatic action. The three dimensional structures of loops can provide essential information for understanding molecular mechanisms behind protein functions. In this article, we develop a novel method for protein loop modeling, where the loop conformations are generated by fragment assembly and analytical loop closure. The fragment assembly method reduces the conformational space drastically, and the analytical loop closure method finds the geometrically consistent loop conformations efficiently. We also derive an analytic formula for the gradient of any analytical function of dihedral angles in the space of closed loops. The gradient can be used to optimize various restraints derived from experiments or databases, for example restraints for preferential interactions between specific residues or for preferred backbone angles. We demonstrate that the current loop modeling method outperforms previous methods that employ residue-based torsion angle maps or different loop closure strategies when tested on two sets of loop targets of lengths ranging from 4 to 12.