الفهرس 
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Abstract
This work aimed to overcome the main drawbacks of some essential anticancer drugs as 5-Fluorouracil (5-FU) by controlled loading with novel drug carriers. This article thesis involves studying of polymerization of (MMA/HEMA) copolymer and MMA-co-HEMA/MWCNTs composite NPs of various monomer feed compositions, drug content, and CNT content to produce biocompatible copolymeric nanoparticles in the nanosized range (less than 100nm) through microemulsion polymerization technique and used as drug carriers.
The microemulsion polymerization technique is characterized by spontaneous formation, ease of manufacture, stability over a wide temperature range, and low viscosity, also, it improves solubilization of bioactive materials. As well, the differential technique is featured with the ability to increase the solid content by using the least amount of emulsifier.
Different techniques have characterized these drug delivery systems such as FT-IR, XRD, TEM, TGA, zeta potential, and a particle size analyzer. Also, the effects of monomer feed composition, 5-FU content, and MWCNTs content on morphological and structural properties, in-vitro 5-FU release, and entrapment efficiency (EE%) have been studied.
The obtained TEM images, XRD charts, and FTIR spectra demonstrate the efficient trapping of drugs in copolymeric and composite NPs. where we note from XRD patterns the disappearance of some drug peak and reduction of the intensity of other peaks which indicate the entrapment of the drug inside the polymer and MWCNTs/copolymer.
TEM image observation suggested that the entrapment of drugs can trigger a significant morphological transformation and appears to be dependent upon several factors including MMA/HEMA monomer feed composition, drug content, and CNTs content. Where, As the monomer feed ratio increases, the particle size is increased and the polymer nanospheres could be loaded with high drug content.
Also, the rise of the drug content from 1:20 to 1:6 leading to an increase in the particle size, and also the integration of CNT increases the particle size.
The colloidal stability of the polymeric nanoparticles was evaluated using zeta potential measurements and appears to be dependent upon MMA/HEMA monomer feed composition, drug content, and CNTs contents. Where, with increasing the HEMA ratio in the latex, the zeta potential value (ζ) increases. Also, the incorporation of functionalized MWCNTs in the drug-loaded polymer increases the zeta potential and enhances the stability against coagulation.
The thermal stability was evaluated for the copolymer using thermal gravimetric analysis (TGA) and was found in the order; drug-loaded copolymer (MMA/HEMA50/50) > free copolymer (MMA/HEMA50/50) > pure 5-FU and the existence of MWCNTs in the drug-loaded polymer enhances the thermal stability and increased with increasing MWCNTs/drug ratio from 1:2 to 2:1.
This work is extended to investigate the feasibility of using the differential microemulsion polymerization technique in the entrapment of drug-forming 5FU-loaded polymeric nanospheres. It is concluded that EE values depend on HEMA content in the monomer feed composition, the drug content, and MWCNTs content.
It was noted that drug EE% was influenced by the monomer feed composition. As the HEMA content increased, the EE% value is increased from 78% to 93% at 5% drug content. Also, the drug EE% is improved from 81% to 90% with increasing the drug content from 5% to 16.6%. In addition to the EE% is significantly enhanced when the drug is loaded on the MWCNTs/(MMA/HEMA50:50) copolymeric nanocomposite and % reached about 99% at high MWCNTs/drug ratio (2:1). Due to the drug filling in the inner cavities of the MWCNTs.
In vitro drug release from the drug-loaded copolymeric nanoparticles into buffer solution appears to be dependent upon many factors including hydrophilic nature of the copolymer, drug solubility, drug content, and MWCNTs content.
The more hydrophilic polymer with a monomer feed composition of MMA/HEMA 50/50 provided faster release rates. On the other hand, the polymer with monomer feed composition as MMA/HEMA 90/10 shows the slowest release rates in both phases. Moreover, drug solubility appeared to play a dominant role in controlling release, where, the drugs are more soluble in the dissolution fluid with pH 7.4 (simulated intestinal fluids) than that with pH 1.2 (simulated gastric fluids), so, the release rates in the simulated intestine fluid, pH7.4, reached higher values compared to the simulated gastric fluid, pH 1.2. The drug release rates reached ” ” ” ” ” ” ” ” " ~ " ” ” ” ” ” ” ” ”70% at pH 1.2 and 85% at pH 7.4 after 2h using the copolymer (50/50).
The small difference in the copolymer release rates at pH 1.2 and pH 7.4 showed that the 5-FU-loaded copolymer can be applied at a wide variety of pH values.
Also, the rate of drug release is influenced by the drug content (a drug to monomer ratio) and it was noted that the copolymer with higher drug loading is faster than that with lower drug loading, moreover, it was noted that the increase of MWCNT relative to the 5-FU drug could improve the controlling of the drug release.
Finally, 5-FU-loaded MWCNTs/copolymer nanocomposite exhibited a significant anti-proliferative effect against CaCo-2, MCF-7, and HepG-2 cell lines, and demonstrated stronger cytotoxicity against the HepG-2 cell line Compared with the other two cell lines.