Transdermální a dermální permeace acyklických nukleosidfosfonátů

• Main Author: Líbalová, Martina
• Other Authors: Vávrová, Kateřina
• Format: Dissertation
• Language: Czech
• Published: 2008
• Online Access: http://www.nusl.cz/ntk/nusl-292600

The objective of this diploma thesis was to determine the transdermal permeation and dermal penetration of acyclic nucleoside phosphonates, a new class of broad-spectrum antivirals. Transport of selected acyclic nucleoside phosphonates through and into porcine skin and the effect of solvents of different polarities was studied in vitro using Franz diffusion cell. We found relatively large differences in the absorption of the individual substances and a marked influence of lipofility of donor vehicle: isopropyl myristate and water. In the second part of this work we studied the influence of pH, concentration in the donor sample and the presence of 1% permeation enhancer 6- dimethylaminohexanoic acid dodecyl ester (DDAK) on the transdermal and dermal delivery of perspective anticancer substance: N6-cyklopropyl-9-[2-(phosphonomethoxy)ethyl]-2,6- diaminopurine (N6-CyPr-PMEDAP). This substance permeates through intact skin barrier relatively slowly and without any dependence on the donor sample pH or its concentration. The addition of 1% permeation enhancer DDAK to the donor sample resulted in an order-of-magnitude increase of permeation and approximately in double increase of penetration at all pH values. The maximum activity of DDAK was observed at pH 6. Increasing the N6-CyPr-PMEDAP concentration in...