9993310
In vitro peptide release from liquid crystalline buccal delivery systems.
Swelling and [D-Ala(2), D-Leu(5)]enkephalin (DADLE) release from the lamellar and cubic liquid crystalline phases of glyceryl monooleate (GMO) were studied using two in vitro methods, a total immersion method and a Franz cell method. The swelling of the lamellar phase and glyceryl monooleate (0% w/w water content) and DADLE release from the liquid crystalline phases were temperature dependent. The swelling ratio was greater at 20 degrees C than 37 degrees C while DADLE release increased at 37 degrees C compared to 20 degrees C for both the lamellar and cubic phases. The water uptake increased dramatically with decreasing initial water content of the liquid crystalline phases. However, DADLE release increased with increasing initial water content, which corresponded to increased viscosity. The swelling and DADLE release profiles obtained using a Franz cell method with a moist nylon membrane to mimic buccal drug release conditions were slower than the total immersion method. These results show that the swelling and DADLE release strongly depended on temperature, the initial water content of the liquid crystalline matrix and the methodology employed for determining the swelling and DADLE release.
21038080
Enhancedex vivo buccal transport of propranolol: Evaluation of phospholipids as permeation enhancers
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.
6921183
The effect of storage conditions on the permeability of porcine buccal mucosa
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.
15555862
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.Results. 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.
Conclusions. 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.
41670121
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.
26009819
Kinetic characterization of swelling of liquid crystalline phases of glyceryl monooleate
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.
31760643
Detection of E. coli in beach water within 1 hour using immunomagnetic separation and ATP bioluminescence.
The contamination of beach waters occurs from the discharge of storm water and sanitary sewer overflows containing faecal material. Additional faecal material derives from discharge of animals and waterfowl. In order to protect public from exposure to faecal-contaminated water, it is required to test enteric indicators in beach water. The problem is that the traditional culture-based methods cannot meet this goal because it takes too long (>24 h), so the results are not available until a day later. A rapid method for testing beach water for Escherichia coli within 1 h has been developed. Immunomagnetic separation (IMS) and ATP bioluminescence were used for selective capture and quantification, respectively. This rapid method was compared to the current method (m-TEC) using beach water samples. The beach samples were prefiltered with a 20 microm pore size filter in order to remove algae, plant debris and large particles. The results showed that the prefiltration step did not trap the bacteria which were present in the original water samples. The prefiltered water was then passed through a 0.45 microm pore size filter for concentration. The deposited bacteria were resuspended and then mixed with superparamagnetic polystyrene beads (diameter of 0.6 microm) that were coated with E. coli antibodies. After IMS, the quantification of the E. coli was done by ATP bioluminescence. The results obtained with IMS-ATP bioluminescence correlated well with the plate count method (Rsq = 0.93). The detection limit of the assay was about 20 CFU/100 mL, which is well below the US EPA limits for recreational water. The entire procedure can be completed in less than 1 hour. The necessary equipment is portable and was tested on-site.
24721977
A Novel Quantitative Measure of Breast Curvature Based on Catenary
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.
7983781
Vessel Diameter Measurement from Intravital Microscopy
The blood vessel diameter is often measured in microcirculation studies to quantify the effects of various stimuli. Intravital video microscopy is used to measure the change in vessel diameter by first recording the video and analyzing it using electronic calipers or by using image shearing technique. Manual measurement using electronic calipers or image shearing is time-consuming and prone to measurement error, and automated measurement can serve as an alternative that is faster and more reliable. In this paper, a new feature-based tracking algorithm is presented for automatically measuring diameter of vessels in intravital video microscopy image sequences. Our method tracks the vessel diameter throughout the entire image sequence once the diameter is marked in the first image. The parameters were calibrated using the intravital videos with manual ground truth measurements. The expriment with 10 synthetic videos and 20 intravital microscopy videos, including 10 fluorescence confocal and 10 non-confocal transmission, shows that the measurement can be performed accurately.
981469
Development of near-infrared fluorophore (NIRF)-labeled activity-based probes for in vivo imaging of legumain.
Asparaginyl endopeptidase, or legumain, is a lysosomal cysteine protease that was originally identified in plants and later found to be involved in antigen presentation in higher eukaryotes. Legumain is also up-regulated in a number of human cancers, and recent studies suggest that it may play important functional roles in the process of tumorigenesis. However, detailed functional studies in relevant animal models of human disease have been hindered by the lack of suitably selective small molecule inhibitors and imaging reagents. Here we present the design, optimization, and in vivo application of fluorescently labeled activity-based probes (ABPs) for legumain. We demonstrate that optimized aza-peptidyl Asn epoxides are highly selective and potent inhibitors that can be readily converted into near-infrared fluorophore-labeled ABPs for whole body, noninvasive imaging applications. We show that these probes specifically label legumain in various normal tissues as well as in solid tumors when applied in vivo. Interestingly, addition of cell-penetrating peptides to the probes enhanced cellular uptake but resulted in increased cross-reactivity toward other lysosomal proteases as the result of their accumulation in lysosomes. Overall, we find that aza-peptidyl Asn ABPs are valuable new tools for the future study of legumain function in more complex models of human disease.
26221478
Unbiased global optimization of Lennard-Jones clusters for N < or =201 using the conformational space annealing method.
We apply the conformational space annealing method to the Lennard-Jones clusters and find all known lowest energy configurations up to 201 atoms, without using extra information of the problem such as the structures of the known global energy minima. In addition, the robustness of the algorithm with respect to the randomness of initial conditions of the problem is demonstrated by ten successful independent runs up to 183 atoms. Our results indicate that this method is a general and yet efficient global optimization algorithm applicable to many systems.