Biomedical Engineering Reference
In-Depth Information
7.4.2 N
ONBIODEGRADABLE
S
YNTHETIC
P
OLYMERS
Nano/microparticles composed of nonbiodegradable hydrophilic polymers are also of much interest
in oral peptide delivery. Polymers such as polyvinyl alcohol (PVA), polyacrylic acid (PAA) and their
derivatives, PEG, polyvinyl pyrrolidone (PVP), etc., are widely investigated for drug-delivery appli-
cations. Unlike biodegradable particles, these systems have restricted cell permeability under nor-
mal circumstances. Most of these systems are designed to release the encapsulated bioactive agent
in the favorable regions of the GIT from where they can be absorbed. A very interesting and promis-
ing approach in oral peptide delivery is the use of bioadhesive or mucoadhesive polymers. The term
bioadhesion refers to the adhesion between two biological materials or between any material and a
biological material. Mucoadhesion refers to the interaction of a material with the mucosal surface
[65]. It was proposed that if the intestinal transit of a delivery system could be delayed by muco-
adhesion, followed by intimate contact at the brush border, might assist the uptake of a peptide or
protein even without the intervention of a direct absorption enhancer. The intimate contact between
a delivery system and the absorbing cell layer will improve both effi ciency and effectiveness of the
system. Mucoadhesive nano/microparticles are potential systems for drug-delivery applications, as
they offer numerous advantages over conventional delivery systems. They can provide an intimate
contact with the mucus layer and thereby enhance bioavailability of the drugs because of a high
surface to volume ratio. Mucoadhesive nano/microparticles were proposed as a novel oral delivery
system for poorly absorbable drugs such as peptides or proteins [66-68].
GIT is coated with a continuous layer of protective secretions known as mucus. Intestinal mucus
layer is composed of water (up to 95% by weight), glycoproteins (0.5-5%), inorganic salts (about 1%
by weight), carbohydrates, and lipids. Mucins represent more than 80% of the organic components
of mucus, and they are O-linked glycoproteins [69,70]. Mucoadhesive delivery systems can penetrate
the mucus layer and bind to the underlying epithelium. Several theories are proposed to explain
the process of mucoadhesion; however, the mechanism involved is not fully elucidated yet. There
are four main theories that describe the possible mechanisms of mucoadhesion: the electronic, the
adsorption, the wetting, and the diffusion theory [71]. The electronic theory assumes that transfer of
electrons occurs between the mucus and the mucoadhesive due to the differences in their electronic
structures. The electron transfer between the mucus and the mucoadhesive leads to the formation
of a double layer of electrical charges at the interface of the mucus and the mucoadhesive. This
interaction results in attraction forces inside the double layer. The adsorption theory concerns the
attraction between the mucus and the mucoadhesive achieved through molecular bonding caused
by secondary forces such as hydrogen and Van der Waals bonds. The resulting attractive forces are
considerably larger than the forces described in the electronic theory. The wetting theory correlates
the surface tension of the mucus and the mucoadhesive with the ability of the mucoadhesive to
swell and spread on the mucus layer and indicates that interfacial energy plays an important role in
mucoadhesion. The wetting theory is signifi cant, since the spreading of the mucoadhesive over the
mucus is a prerequisite for the validity of all the other theories. The diffusion theory concerns the
interpenetration to a suffi cient depth and physical entanglement of the protein and polymer chains
of the mucus and the mucoadhesive, depending on their molecular weight, degree of cross-linking,
chain length, fl exibility, and spatial conformation [72-74].
There is no unifi ed theory to explain the process of mucoadhesion. The total phenomenon of
mucoadhesion is a combined result of all these theories. First, the polymer gets wet and swells
(wetting theory) followed by the noncovalent (physical) bonds created within the mucus-polymer
interface (electronic and adsorption theory). Then, the polymer and protein chains interpene-
trate (diffusion theory) and entangle together to form further noncovalent (physical) and covalent
(chemical) bonds (electronic and adsorption theory). Hydrophilic polymers usually display the
property of mucoadhesion because of their large molecular weight and ability to interpenetrate and
entangle through mucus gel layer. The presence of hydrophilic functional groups is an important
