2H NMR evidence for dynamic disorder in human skin induced by the penetration enhancer azone

Penetration enhancers mediate trans-dermal drug delivery. The penetration enhancer dodecyl-azacycloheptanone (Azone(R)) was characterized in situ with H-2 NMR on human stratum corneum treated with either uniformly deuterated Azone(R) or penetration enhancer with only the entire chain deuterated, in both cases in propylene glycol. The H-2 NMR spectrum at ambient temperature constitutes a single narrow line only 180 Hz wide. This contrasts with the complex lineshapes 1-25 kHz wide commonly observed for methylene deuterons of lipids in a bilayer gel phase, Hence there is no evidence for differences in orientational behaviour between different deuterons at ambient temperature. The narrow line translates into a low overall order parameter S-CD Solid state NMR/Biophysical Organic Chemistr

Lysophosphatidylcholine as an adjuvant for lentiviral vector mediated gene transfer to airway epithelium: effect of acyl chain length

Extent: 11p.Background Poor gene transfer efficiency has been a major problem in developing an effective gene therapy for cystic fibrosis (CF) airway disease. Lysophosphatidylcholine (LPC), a natural airway surfactant, can enhance viral gene transfer in animal models. We examined the electrophysiological and physical effect of airway pre-treatment with variants of LPC on lentiviral (LV) vector gene transfer efficiency in murine nasal airways in vivo. Methods Gene transfer was assessed after 1 week following nasal instillations of a VSV-G pseudotype LV vector pre-treated with a low and high dose of LPC variants. The electrophysiological effects of a range of LPC variants were assessed by nasal transepithelial potential difference measurements (TPD) to determine tight junction permeability. Any physical changes to the epithelium from administration of the LPC variants were noted by histological methods in airway tissue harvested after 1 hour. Results Gene transduction was significantly greater compared to control (PBS) for our standard LPC (palmitoyl/stearoyl mixture) treatment and for the majority of the other LPC variants with longer acyl chain lengths. The LPC variant heptadecanoyl also produced significantly greater LV gene transfer compared to our standard LPC mixture. LV gene transfer and the transepithelial depolarization produced by the 0.1% LPC variants at 1 hour were strongly correlated (r2 = 0.94), but at the 1% concentration the correlation was less strong (r2 = 0.59). LPC variants that displayed minor to moderate levels of disruption to the airway epithelium were clearly associated with higher LV gene transfer. Conclusions These findings show the LPC variants effect on airway barrier function and their correlation to the effectiveness of gene expression. The enhanced expression produced by a number of LPC variants should provide new options for preclinical development of efficient airway gene transfer techniques.Patricia Cmielewski, Don S. Anson and David W. Parson

In Vivo Methods for the Assessment of Topical Drug Bioavailability

This paper reviews some current methods for the in vivo assessment of local cutaneous bioavailability in humans after topical drug application. After an introduction discussing the importance of local drug bioavailability assessment and the limitations of model-based predictions, the focus turns to the relevance of experimental studies. The available techniques are then reviewed in detail, with particular emphasis on the tape stripping and microdialysis methodologies. Other less developed techniques, including the skin biopsy, suction blister, follicle removal and confocal Raman spectroscopy techniques are also described

The Gold Star Journal, 2011 Edition

The Gold Star Journal showcases the excellence of every academic department at The Citadel through the publication of cross-disciplinary, nonfiction papers and creativity and ingenuity through the publication of photographs and photo stories. This edition's featured papers are: The Method Behind His Madness ; Race and Policing: An Assessment of Cultural Problems ; Racing Towards a Brave New World ; Wilfred Owen’s Brutal Honesty on the Wartime Experience ; The Evolution of Christianity in the American Society ; The Building of Braddock’s Road