الفهرس 
General introductionOnly 14 pages are availabe for public view
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Abstract
- The thesis content can be portrayed briefly as five chapters:
Chapter (I): General introduction:
- This chapter contains general introduction regarding the work done and includes two parts:
Part (I): It contains an overview about nanomedicine. The drug delivery systems (DDSs)
based on nanomedicine proofed high potential and wide applicability that have distinct
features related to nanosized property. Enhancement of bioavailability and
pharmacokinetics after oral administration via utility of natural/synthetic biodegradable
polymeric nanomaterials. Improving biocompatibility, safety, enhanced permeability,
better retention time, lower toxicity, and efficient transportation of drugs to desired
tissues or cells. These nanomaterials are based on different types including metallic and
polymeric Nanomedicine that can hybride with each other to gain new and unique
features increase the efficiency of drug delivery and decrease patient compliance.
Nanomaterials especially electrospinning nanofiber mats have a great potential in DDSs
that reveals a sophisticated manufacturing technique.
Part (II): It illustrates the main principles and components of ISEs, wearable and
integrated multi-parameter sensors and the promising real-time on-body monitoring, the
different mechanisms of solid contact transduction types of ISEs, and novel designs for
potentiometric sensors.
Chapter (II): characteristics and Cell Toxicity Assessment of Venlafaxine -
Electrospun Composite Nanofibers for Buccal Drug Delivery Systems
In this chapter, electrospun nanofiber mats were developed as a new vehicle of drug
delivery systems (DDSs). Electrospinning is a highly sophisticated and robust technique
used in the fabrication of ultrafine fibers from different electrostatic fluids. This research
work focuses on blending poly (lactic acid) (PLA) and poly (ε-caprolactone) (PCL) at a
ratio of (1:1) fixed at 10 wt%/v. Venlafaxine was loaded on PLA/PCL blend nanofibers.
This was followed by in -vitro studies in phosphate buffer (pH7.4), ex-vivo studies using
chicken pouch mucosa as a fitted buccal model, and histological examination of this
mucosa to confirm the release of the drug and its flux and permeability. Also,
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mathematical models for drug release kinetics were calculated and exhibited the high
linearity of Higuchi and Korsmeyer-Peppas models. Highly fitting models suggest the
drug release mechanism is close to Fickian diffusion approaches of drug release.
Characterization of electrospun nanofibers was also applied using a scanning electron
microscope (SEM), fourier transforms infrared (FTIR) X-ray diffraction (XRD), and
differential Scanning Calorimetry (DSC). SEM morphologies refer to free-beads, smooth,
very narrow, and uniform electrospun fibrous structures of PLA, PCL, and PLA/PCL
nanofiber mats. XRD patterns are in a good agreement with drug release profiles. These
results manifest the PLA is more amorphous than PCL and PLA/PCL composite NFs
enhanced the drug therapeutic profile of sustained VEN release. Furthermore, the
cytotoxic effect of the pure VEN, plain NFs, and medicated NFs (F3) was evaluated in
liver cancer (Huh-7), oral epithelial cell (OEC), green monkey kidney (Vero) cells using
WST-1 assay. The cell viability showed that more than 80% cells were viable after 48 h
of incubation and that PLA/PCL composite NFs are non-toxic and cyto-compatible.
Chapter (III): Cost-effective solid contact potentiometric sensors based on imprinted
receptors for fluvoxamine determination:
In this chapter, a simple, efficient, and reliable analytical method was developed and
used for the determination of the fluvoxamine drug (FLV) in pharmaceutical preparations
and biological fluids. The method is based on the cost-effective screen-printed platform
for the potential transduction of the drug. Host-tailored molecular imprinting polymer
(MIP) was integrated with the potentiometric platform as a recognition receptor, in which
FLV, acrylamide (AAm), ethylene glycol dimethacrylate (EGDMA), and acetonitrile
were used as a template, functional monomer, crosslinker, and solvent, respectively. MIP
particles were dispersed in plasticized poly (vinyl chloride) (PVC) and the membrane was
drop-casted on a carbon screen-printed electrode. The MIP, in addition to non-imprinted
polymers (NIP), was characterized and the binding experiment revealed high affinity and
adsorption capacity of MIP towards FLV. The proposed sensor displayed near-nernstian
cationic slope of 55.0 ± 0.8 mV/decade (r2
= 0.999) with a low detection limit of 4.8 ×
10−6 mol/L over a wide pH range (3.0–8.5). The electrochemical features of the proposed
sensors including electrochemical impedance spectroscopy (EIS) and
chronopotentiometry measurements (CP) in the presence of multi-walled carbon
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nanotubes (MWCNTs) as a solid contact transducer were also investigated. The
applications of the proposed sensor for the determination of FLV in different dosage
forms with recovery values (98.8%–101.9%) and (97.4%–101.1%), respectively
compared with the reference HPLC method with accepted F and t-student tests values at
the 95% confidence level.
Chapter (IV): Imprinted polymeric beads-based screen-printed potentiometric
platforms modified with multi-walled carbon nanotubes (MWCNTs) for selective
recognition of fluoxetine:
In this chapter, we present a new validated potentiometric method for fluoxetine (FLX)
drug monitoring. The method is based on the integration of molecular imprinting polymer
(MIP) beads as sensory elements with modified screen-printed solid contact ion-selective
electrodes (ISEs). A multi-walled carbon nanotube (MWCNT) was used as a
nanomaterial for the ion-to-electron transduction process. The prepared MIP beads
depend on the use of acrylamide (AAm) and ethylene glycol dimethacrylic acid
(EGDMA) as a functional monomer and cross-linker, respectively. The sensor revealed a
stable response with a Nernstian slope of 58.9 ± 0.2 mV/decade and a detection limit of
2.1 × 10−6 mol/L in 10 mmol/L acetate buffer of pH 4.5. The presented miniaturized
sensors revealed good selectivity towards FLX over many organic and inorganic cations,
as well as some additives encountered in the pharmaceutical preparations. Repeatability,
reproducibility, and stability have been studied to evaluate the analytical features of the
presented sensors. These sensors were successfully applied for FLX assessment in
different pharmaceutical formulations collected from the Egyptian local market. The
obtained results agreed well with the acceptable recovery percentage and were better than
those obtained by other previously reported routine methods.
Chapter (V): A comparative study of transduction mechanisms of Multi-Walled Carbon
Nanotubes (MWCNTs), Polyaniline and Ferrocene solid contact ISEs for Venlafaxine
monitoring:
In this chapter, a screen-printed electrode (SPE) was fabricated for the determination of
venlafaxine hydrochloride (VEN) based on the use of venlafaxine- tetraphenylborate
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(VEN-TPB-
) as the electroactive substance. The proposed sensor was applied with PVC
membrane plasticized with o-NPOE. The active sensing part of the sensor was VENTPBion-pair complex. The different transducers were used such as multi-walled carbon
nanotube (MWCNT), poly(aniline) (PANI), and ferrocene. The applied sensor based on
MWCNT showed the best results with a cationic near –Nernestian slope of 56.1±0.8
mV/decade with a detection limit of 3.8 ×10-6 mol/L (r2
=0.999). Also, the sensor showed
high selectivity and applicability of the determination of VEN in different dosage forms.
Besides, chronopotentiometry (CP) and electrochemical impedance spectroscopy (EIS)
measurements were studied and showed the difference between the three applied
transducers. The potential drift (∆E/∆t) order based on sensor type was VEN-TPB-
<ferrocene /VEN-TPB-
<PANI/ VEN-TPB-
< MWCNT/ VEN-TPB- with values 97.7,
61.2, 41.6, and 34.6 µV/s respectively. Furthermore, the highest double layer was
exhibited from the MWCNT sensor (16.3 µF). The calculated measurements of Rb were
assigned as 0.4, 0.08, 0.3, and 0.3 MΩ for the sensor I, II, III, and IV, respectively.
MWCNT sensor type exhibited the lowest resistance. The transduction occurs through
different mechanisms as a redox reaction that is exhibited in the case of PANI and
ferrocene sensor types and a double layer formation in the case of MWCNT sensor type.
CP and EIS results showed that MWCNT based sensor had the most sophisticated and
durable features. Method validation was also studied by measuring the detection limit,
linearity range, robustness, accuracy, ruggedness, precision, repeatability, and
reproducibility