ABSTRACT
Antimicrobial therapy remains to be the most important method of wound infection treatment. Systemically administered antimicrobials may not achieve therapeutic level in wound. On the other hand, in the absence of surgical debridement [due to any reason], most topically applied antimicrobials cannot penetrate the wound in therapeutic amount due to the presence of eschar. Burn eschar is a proteinous structure with some lipid components in which proteins seems to play an important role in the barrier effects of eschar. Therefore, in this study the effect of protein-acting enhancer [trypsin] on permeation of hydrophilic model drug [clindamycin phosphate] was investigated
To perform this investigation, permeation of saturated clindamycin phosphate was studied at 32 degreeC through trypsin treated and untreated eschar samples for 12 h using home-made static diffusion cells. Third-degree burn eschar samples were separated at the time of surgical debridement [7-14 days post burn] from burned patients. Before each experiment, eschar was hydrated for 12 h and samples were then treated with trypsin solution [1%, w/v] for 4 and 24 h. Clindamycin was measured by a HPLC method developed here
Results showed that after trypsin-treatment for 4 and 24 h, clindamycin phosphate permeation flux was increased significantly by about 1.5 and 2 times and permeation lag-time was decreased by about 2 and 1.3 times respectively
The present results show that permeation of drugs through burn eschar can be increased considerably by trypsin
ABSTRACT
The current methods for treatment of cancers are inadequate and more specific methods such as gene therapy are in progress. Among different vehicles, cationic liposomes are frequently used for delivery of genetic material. This investigation aims to prepare and optimize DOTAP cationic liposomes containing an antisense oligonuclotide [AsODN] against protein kinase C alpha in non-small cells lung cancer [NSCLC]
To perform this investigation, two different methods of ethanol injection and thin film hydration were used to prepare AsODN-loaded DOTAP liposomes
The formulated liposomes were then evaluated for their morphology, particle size, zeta potential and encapsulation efficiency, and the best formulation was chosen. In-vitro growth inhibitory effect of encapsulated ODN on A549 cells were evaluated by MTT and colonogenic assay. The physical and serum stability of liposomal ODN were also evaluated
Thin film hydration method resulted in large liposomes that required downsizing by extrusion with an encapsulation efficiency of 13%. Ethanol injection, in a single step gave liposomes with a small size of 115 nm and an encapsulation efficiency of around 90% which were physically stable for 6 months. The optimized liposome could protect oligonucleotides from degradation by nuclease. Cell studies showed a 20% sequence-specific inhibition of cell growth in MTT assay and revealed an LC[50] of 103 nM in colonogenic studies
In conclusion, ethanol injection was able to provide suitable liposomes from the permanently charged DOTAP. Also the resulted liposomes were able to inhibit the growth of lung cancer cells