الفهرس 
Formulation and Evaluation of Nanoparticles containing Certain Anticancer drug
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Abstract
The pre-formulation study of fluorouracil with different four lipids (cholesterol, compritol®, stearic acid, GMS) was investigated by DSC analysis, XRD patterns, and FTIR. DSC result showed that fluorouracil peak (Tm) (280°C) was present in all physical mixtures with mentioned lipids.
In the case of drug-cholesterol blended mixture, Tm peak of the drug was present with a minor change, while the drug-compritol® blended mixture, Tm peak of the drug was shifted, indicating that the drug was completely immersed inside this lipid matrix. In the case of drug-stearic acid and drug-GMS blended mixtures, the peak was present with small changes.
XRD results showed that fluorouracil crystalline state was still found in all physical mixtures of drug with lipids.
In the case of drug-blended mixtures, all peaks of the drug were present except in XRD of fluorouracil -compritol® blended mixtures showed that numerous distinct peaks disappeared while other peaks appeared in low intensities indicating that the drug was in a non-crystalline state (amorphous state). FTIR spectrum of physical mixtures of fluorouracil with mentioned lipids showed that all characteristic peaks of the drug appeared with minor changes in position.
In the case of drug blended mixture with (cholesterol, GMS, and compritol®) all functional peaks of the drug were present thus showing no significant physicochemical interaction between the drug and these lipids. While 5-FU with stearic acid blended mixture showed the absence of N-H peak at 3136 cm-1.
For this study, GMS was chosen for the formulation of solid lipid nanoparticles and additional studies.
A new kind of solid lipid nanoparticles was prepared based on high shear homogenization technique for preparation using glycerol mono stearate as lipid matrix and tween 80 as surfactant. (1:2) w/w GMS- tween 80 solid lipid nanoparticles with silver at speed 8000 for five minutes and using dimethyl sulfoxide as organic solvent .Tem reveals that formed SLNS are spherical in shape with uniform structure and entrapment efficiency was measured about 60%. Addition of silver to the optimum formula and % entrapment efficiency was 70%. In vitro drug release found that 77% of 5-fluorouracil was released in comparison to formula (92% within 3 hours) without silver indication that silver had role in improvement of drug release.
This formula was chosen for further study. SRB(sulphorhodamine -B assay) assay reveals that when drug loaded in solid lipid nanoparticles with silver become more potent with IC 50% in MCF7 and in PC3 less than free drug (2.2 um and 2 um) respectively. Pharmacokinetics parameters of both free drug and drug loaded were deduced in this study. It could be concluded that 5-fluorouarcil-GMS- silver (1:4 w/w) is a better system for extended release of the water soluble 5-fluorouracil compared to drug alone. Sustained releases properties of GMS-5fluororacil-silver suggest that it could provide a valuable sustained release dosage form of water soluble drugs like 5-fluorouracil