الفهرس 
Introduction and Literature ReviewOnly 14 pages are availabe for public view
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Abstract
Much effort has been devoted to nanotechnology, and developing polymer based nanostructures stimulated by the fact that at nanoscale level (1-100 nm), the properties of a material including (thermal stability, mechanical strength, optical and magnetic properties, electrical conductivity, elasticity, and permeability) can change dramatically without altering the material itself which is known as the ”nanoeffect”.
Polymer nanocomposites are hybrid materials in which inorganic filler is dispersed in the polymer matrix at the nanometer scale. Polymer nanocomposites can be prepared via different methods that can be classified into: melt compounding, solution dispersion and in situ polymerization.
Among the various processing techniques for polymer nanocomposites, electrospinning is a versatile and effective technique for production of polymeric nanofibers with different diameters ranging from submicrons to nanoscale and many polymers have been effectively transformed into fibers from solution or melt form. Motivation for interest in polymeric nanofibers is due to their high surface area to volume ratio, enhanced mechanical properties, porosity, flexibility, and mimicry of extracellular matrix. These outstanding features make polymeric nanofibers promising candidates for developing functionalized drug delivery systems (DDS) that are capable of encapsulating therapeutics along with their release in a controlled and sustained pattern.
This work aims at production of nanofibrous materials based on polymer nanocomposites by electrospinning technique, and investigation of the prepared nanocomposite nanofibrers as drug vehicles for transdermal delivery. To achieve this goal, several steps were followed:
In the first section, clay was organically modified through ion exchange reaction with various loadings of the long alkyl chain quaternary ammonium surfactant, tallow to replace the hydrophilic cations such as (Na+, and Ca2+) present in clay interlayers.
Neat PA6 nanofibers were produced by electrospinning of PA6 solutions at various concentrations ranging from 30% to 45% (w/v) to investigate the effect of polymer solution concentration on the morphological properties of the obtained nanofibers. Then various contents of TMC1:1 were incorporated into the electrospinning of PA6 solution (35% w/v) to fabricate PA6/TMC nanocomposite nanofibers.
Successful interlayer modification of clay was confirmed via XRD, FT-IR, TGA, surface charge, and SEM images. XRD results showed gradual increase in d-spacing of clay with increasing tallow content; the basal spacing of pristine clay was 14.32 and increased to 39.35 for TMC 1:1. FTIR spectra of modified clay showed the characteristic peaks at 2917 cm-1, and 2850 cm-1 due to CH2 asymmetric and symmetric vibrations respectively which were completely absent in the spectra of pristine clay. from TGA results, it was noticed that the onset decomposition temperature of TMC1:1 was higher than that of pristine clay. However modified clay exhibited significant mass loss between 270℃ and 450℃ which was much higher than pristine clay that showed prolonged stability. The zeta potential of pristine clay was measured as (-30 mV), while after modification with tallow at (1:1 tallow/clay w/w ratio), the zeta potential changed to (-17 mV) confirming the effect of modifier on the surface charge of clay. SEM images revealed significant morphological changes between unmodified and modified clay; pristine clay appeared as large aggregated particles, while TMC1:1 showed reduced aggregation and packing density of layers.
In electrospinning of neat PA6 solutions, it was observed that, polymer solution concentration had great influence on nanofibers morphology, and average diameters. The lowest concentration of PA6 solution (30% w/v) resulted in beaded nanofibers with several breaks up, whereas with increasing the concentration to (35% w/v), homogenous, and beads free fibers with average diameter of 74.2 ± 4.42 nm were obtained. Further increase of polymer solution concentration to (45% w/v) produced ribbon like structures with submicron diameters of about 425.9 ± 69.46 nm due to increased viscosity of polymer solution and reduced flowabilty during the electrospinning process. Addition of various loadings of TMC1:1 (e.g. 0.5%,
0.75%, and 1% w/w) to (35% w/v) PA6 solution had dramatic effect on fiber morphology and average diameters: addition of 0.5% w/w of TMC1:1 produced smooth fibers with 105± 12.53 nm average diameter while further increasing TMC1:1 content, steadily decreased the fibers diameter to 78.5± 3.92 nm for PA6/TMC nanocompsite fibers containing 1% TMC.
In addition, TGA results indicated that PA6/TMC1:1 nanocomposite fibers with 1% TMC1:1 had higher decomposition temperatures and slower mass loss rate compared to neat PA6 nanofibers. In order to investigate the dispersion of TMC1:1 into polymer matrix, (SAXRD) was performed and suggested formation of intercalated nanostructures which was further confirmed from TEM images and the mechanical test that showed enhancement of tensile stress, tensile strain, and young’s modulus of the nanocomposite nanofibers.
In the second section, PA6/TMC1:1 nanocomposite fibrous mat with 1% TMC1:1 was used for drug loading through post spinning modification approach. To achieve this goal, two types of post spinning modification were followed:
The nanofibrous mat was coupled with hydrogels composed of sodium alginate (NaAlg), polyvinyl alcohol (PVA) or a mixture of both to produce bilayer hybrid drug delivery templates. The hydrogel precursors were cross-linked either ionically by CaCl2 solution or physically by repeated freezing-thawing cycles (cryogenic approach) to avoid toxic crosslinking agents. Doxycyline hydrochloride as a potent antibiotic drug was loaded into ionically cross-linked alginate hydrogel layer by adsorption method, while it was added directly into the hydrogel percursors of PVA or mixtures of PVA and NaAlg before inducing crosslinking (active loading method). The results indicated that, with increasing NaAlg content, the gel fraction gradually decreased from 90 ± 1.84% for neat PVA to 70.57 ± 1.65 at 30% w/w NaAlg content, while the swelling behavior significantly increased by increasing NaAlg content; the swelling ratio increased from 211.37± 10.41% for neat PVA to 345 ± 8.71% after addition of 30% w/w NaAlg. SEM images of surface and cross section of drug loaded PA6/TMC1:1 nanofibrous mat coupled with hydrogels showed that, the fibrous layer was completely covered with the hydrogel layer and porous structure with varying pore size was observed in the cross section images of fibers-PVA and fibers-PVA/NaAlg 10% w/w. The drug release profiles in (PBS) at pH 7.4 and in acetate buffer (pH 5.5) were controlled mainly by structural factors. Initial burst release was observed for nanofibers-CaAlg (ionically crosslinked) and a relatively slow release rate was achieved from nanofibers - physically crosslinked PVA, or mixture of PVA-NaAlg.
In the other type, the surface of the nanofibrous mat was chemically modified through grafting copolymerization of acrylamide using potassium persulfate and sodium hydrogen sulfite redox initiation system. The grafting parameters including (initiator and monomer concentration, temperature, and duration of reaction) were studied. Methylene bisacrylamide, as a crosslinker was added to obtain crosslinked polyacrylamide hydrogel layer grafted to the nanofibers.
The optimum grafting conditions were as follow: initiator concentration, 20mM/l; monomer concentration, 30% w/v; temperature, 60 ℃; reaction time, 1h. The chemical structure of grafted nanofibrous mat was analyzed by ATR-FTIR that showed the peak at 1536 cm-1 due to the combined absorption of -NH and C-N was weakened after the grafting reaction indicating the involvement of the –NH groups of PA6 in the grafting reaction. TGA data showed decreased onset degradation temperature after grafting reaction. However, the char residue was much higher than that of ungrafted nanofibers. SEM images showed that the surface of polyacrylamide grafted mat (76% grafting ratio) was rough and less uniform and the average fiber diameter increased from 78.5± 3.92 nm to 139 ± 28.36 nm after grafting reaction.
The drug was loaded to crosslinked polyacrylamide grafted nanofibers by swelling diffusion method and the loading content was measured as 100 ± 11.98 mg/gm. In vitro drug release studies showed that the drug released fast in both PBS (pH 7.4) and acetate buffer (pH 5.5) and initial burst release was
observed in the first two hours. A total release of 94.56 ± 1 % and 89 ± 0.79 % was achieved in PBS and acetate buffers respectively.
Furthermore, the release mechanisms were investigated through modeling of the release data. In addition, the antimicrobial evaluation of both types of the as prepared drug delivery systems against E. coli as example of gram negative bacteria and S. aureus as gram positive beacteria confirmed that the loaded drug retained its antimicrobial activity and the toxicity test of these systems proved to be nontoxic.
The aforementioned results indicate the great potential of the prepared drug delivery systems for transdermal patches as it showed effective drug release in both of acetate buffer (pH 5.5, skin pH), and PBS (pH 7.4, Physiological pH).