الفهرس 
Theoretical background and literature reviewOnly 14 pages are availabe for public view
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Abstract
5. Summary and Conclusion
5.1. Summary
Developing a new drug delivery system tends to trigger the growing of tick’s infestation in cattle as it leads to inflammation of the skin and continuous rubbing which lead to skin injury and cause economic problems. This study aims at preparation and characterization of a novel drug delivery system based on functionalized MWCNTs with TEOS using sol-gel technique, in the presence of ABZ, IVM and Cav and/or β-CD which were used as a drug models. The prepared materials were characterized using FTIR, TEM, particle size distribution analysis using DLS technique and TGA. In vitro kinetic release study of the immobilized ABZ, IVM and Cav were carried out in PBS at pH 2.5 at 37°C using the different mathematical models (zero order, first order, hixson- Crowell and higuchi). Moreover, in vitro cytotoxic effect on the normal fibroblast cell line (BHK- 21) using SRB assay, was also investigated.
The results indicated that FTIR, TGA, TEM and particle size analysis of the prepared materials showed the successful immobilization of ABZ, IVM and Cav onto the functionalized MWCNTs through covalent bonds with a particle size range of around 495, 395 and 475 nm in the case of ABZ, IVM and Cav respectively. The cumulative released resulted in a biphasic release behavior with a rapid initial burst phase with release percentages of about 66.94, 72.79 and 65.25 % for ABZ, IVM and Cav respectively and the release was increased by the addition of β-CD, 88.88, 85.4 and 70.94% for ABZ, IVM and Cav respectively. It can be concluded that the most effective drug model was in the following order IVM> Cav> ABZ.
Moreover, in vitro cytotoxic study revealed that they had low toxic effect against BHK-21 cell line at different concentrations (12.5, 25, 50 and 100 µg/mL) in comparison with the free drugs. The results showed different mortality percentages of the dead cell also Ox-MWCNTs had a low toxicity of about 1.7 and 3.4 % at 12.5 and 100 µg/mL concentrations respectively. TEOS showed high toxicity more than Ox-MWCNTs with gradient increase in number of mortalities with increasing in concentration. It shows high mortality at 100 µg/mL about 6.9%. ABZ showed high mortality percentage at concentration 100 µg/mL relative to that in case of other drugs (IVM and Cav) about 77.8% while after immobilization onto Ox-MWCNTs and Ox-MWCNTs/β-CD the mortality percentage was decreased to about 23.7 and 22.5% respectively. On the other hand, the free IVM and Cav exhibited low mortality percentage about 8.5 and 7.8 %, respectively. While after immobilization onto Ox-MWCNTs and Ox-MWCNTs/β-CD, the mortality had no significant changed and so by changing the formulations. It was noticed that development occurred in its solubility with low toxicity at 100 µg/mL was about 4.5 and 3.7% after immobilization onto Ox-MWCNTs and Ox-MWCNTs/β-CD, respectively. The free drug Cav had mortality percentage at 100 µg/mL about 7.8%, while after immobilization; the mortality was decreased to 4.4% and 1% in case of using Ox-MWCNTs and Ox-MWCNTs/β-CD, respectively.
In addition, the immobilized ABZ, IVM and Cav onto Ox-MWCNTs and Ox-MWCNTs/β-CD formulations after 12, 48 and 72 hr. of exposure displayed a high tick mortality percentage against the cattle tick R. (B.) annulatus females. The adulticidal activity of the immobilized ABZ, IVM and Cav onto Ox-MWCNTs and Ox-MWCNTs/ β-CD formulations at different concentrations (50, 100, 150, 200, 250 and 300 μg/mL induced a significant (P<0.001) lethal effect on adult female ticks. The larvicidal efficacy of the prepared materials resulted in 93 % after 72h at 250 μg/mL for immobilized ABZ while immobilization using β-CD resulted in a complete larval mortality (100 %) within 72 h of exposure at concentration of about 250 μg/mL and this due to the increase of solubility in presence of β-CD. While in case of immobilized IVM and Cav complete larval mortality (100 %) within 72 h of exposure at concentration about 250 μg/mL and the mortality percentage increased at lower time by using β-CD at 12h and 48h. on the other hand, at low concentration (50 μg/mL), the mortality was about 10±0.0e, 16.7±33e and 26.7±3.3d % for immobilized ABZ, IVM and Cav respectively but after addition of β-CD the mortality percentage increased to 20±0.0d, 33.3±3.3e and 40.0±0.0b for immobilized ABZ, IVM and Cav respectively. In the present study from lethal concentration for 50% (LC50) the immobilized IVM showed the lowest (LC50) (96.4) followed by the immobilized Cav (120.6) and then the immobilized ABZ (165.4) using Ox-MWCNTs/ β-CD formulations. These results indicated that IVM exhibited high activity against R. (B.) annulatus female ticks, especially in case of using β-CD as carrier. This may be due to increasing the drug solubility.
5.2. Conclusion
It can be concluded that the immobilized ABZ, IVM and Cav onto functionalized MWCNTs using sol gel technique improved the drug activity and reduced cytotoxicity with sustained release performance in comparison with other drug delivery systems. Besides, FTIR, TGA, TEM and particle size analysis proved that ABZ, IVM and Cav were attached successfully with the side chains of the oxidized MWCNTs via covalent rather than adsorption binding. The presence of the oxidized MWCNTs decreased the cytotoxicity of the immobilized drug models against BHK-21 cell line.
Moreover, the cumulative ABZ, IVM and Cav released profile exhibited a burst release behavior up to 50 % after 30 min at concentration about 300 mg/mL the oxidized MWCNTs can acts as a promising carrier for antihelmences drugs with low toxicity against normal cells. In respect of the originality, the current study provides, for the first time data about immobilization of IVM and Cav on Ox-MWCNTs, and their physicochemical and in vitro toxicity characteristics using a normal fibroblast cell and R. annulatus female ticks.