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Zainab A. Alobaidy

Enhancing Oral Delivery of Glutathione Using Chitosan
Zainab A. Alobaidy
A Thesis Submitted in Partial Fulfillment of the
Requirement for the Degree of Master of Sciences
University of Petra
Faculty of Pharmacy and Medical Sciences
December 13
Chapter One: Introduction
Chapter One
Introduction and Literature Review
Chapter One: Introduction
In past years biotechnologically derived drugs, including peptides and proteins, have
become the focus of attention of drug development efforts (Tang et al., 2004). The
destiny of biotechnologically derived drugs after in vivo administration is usually
monitored by the standard pharmacokinetic factors namely; absorption, distribution,
metabolism, and elimination (ADME) (Barratt, 2003).
Having adequate bioavailability, which is defined as “the ratio of drug accumulation
at its site of action to the amount delivered to the body” is considered a significant
limitation in the use of protein or peptide biologics as treatments (Hamman, et al.,
Developing and finding a polypeptide drug delivery via the gastrointestinal tract has
been a continuous challenge attributed to their unfavorable physicochemical
properties, which includes poor absorption, enzymatic degradation, poor membrane
permeability in the gastrointestinal tract, unfolding of the protein, and their relatively
short half life post absorption (Vincent and Duncan, 2006). Beside a variety of
physiological and morphological factors in the gastrointestinal tract, proteolytic
enzymes in the gut lumen like pepsin, trypsin and chymotrypsin along with
proteolytic enzymes at the brush border membrane (endopeptidases); the bacterial gut
flora; the mucus layer and epithelial cell lining became barriers against protein or
peptide delivery (Lee et al., 1990).
Such barriers led to the necessity of developing special delivery systems that can
improve the oral bioavailability of therapeutic proteins from less than 1% to at least
30-50 % (Shaji and Patole, 2008). Despite various attempts, however, no clinically
efficient oral formulations have been developed yet (Park et al., 2011).
Chapter One: Introduction
Nanoparticles delivery systems have many advantages including the high in vivo
stability, long-term payload capacity release, and the ability of permeating through
small capillaries and cellular compartments (Yih and Al-Fandi, 2006). Moreover,
using nanosized particles could enhance the drug’s therapeutic index, modulate its
pharmacokinetic and biodistribution, and aid in forming sustained release reservoirs
(Herman et al., 1997).
The primary demands for a typical delivery of a nanoparticle include: be small sized
(50–200 nm), have high loading capacity, slow complex dissociation in vivo, and
target optimization to the desired tissue with limited absorption by other tissues. The
development of formulations that can integrate these characteristics while considering
the cost and the simplicity of the design is essential for effective delivery systems (De
Jong and Borm, 2008.).