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II- Mucoadhesive
• Buccal drug delivery
• Sublingual drug delivery.
• Nasal drug delivery.
• Ocular drug delivery.
• Gastro intestinal drug delivery.
• Vaginal drug delivery.
• Rectal drug delivery.
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Mucosal membranes
- These are moist membranes (inner epithelial Cell lining) that line passageways and
structures in the body that lead to the outside environment such as the mouth, respiratory
tract, gastrointestinal tract, nose and vagina.
- They secrete a viscous or viscoelastic fluid known as mucus (secreted by goblet cells),
which acts as a protective barrier and also lubricates the mucosal membrane.
- The primary constituent of mucus is a glycoprotein known as mucin (an anionic
polyelectrolyte ) as well as water, free protein and inorganic salts.
- Adhesion : is the bond produced by interaction between an adhesive and a surface.
- Bioadhesion : is the state of bond formation in which either adhesive or surface is of
biological origin.
- Mucoahesion: If substance (polymer) adhere to Biological mucosal layers.
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Definition of a Bioadhesive Polymer

 A polymer is a substance formed by the linkage of a large number of small

molecules known as monomers.

 A bioadhesive polymer is a synthetic or natural polymer which binds to
biological substrates such as mucosal membrane
 Such polymers are sometimes referred to as biological ‘glues’ because they are

incorporated into drugs to enable the drugs to bind to their target tissues.

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Characteristics of Bioadhesive polymers

In order for polymers to adhere to mucosal surfaces or epithelial cell they must ideally possess certain
characteristics:
 Flexibility- The flexibility of bioadhesive polymers is important because it controls the extent of the
interpenetration between the polymers and mucosal/epithelial surfaces.
 Hydrophilicity – Polymers that are hydrophilic in nature are able to form strong adhesive bonds with
mucosal membranes because the mucus layer contains large amounts of water.
 Hydrogen bonding – Hydrogen bonding between the entangled polymer chains forms strong adhesive
bonds, therefore the presence of hydrogen bond – forming groups such as OH and COOH groups are
vital in large quantities.
 High molecular weight – Polymers with a high molecular weight are desirable because they provide
more available bonding sites.
 Surface tensions – Surface tensions are needed to spread the bioadhesive polymer into the mucosal
layer epithelial surface.
 Strong anionic charges.(cellulose derivatives) but some cationic (e.g., Chitosan) 28-Feb-19
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Mechanisms of bioadhesion
The mechanisms responsible for the formation of bioadhesive bonds are
not fully known, however most research has described bioadhesive bond
formation as a three step process.
Step 1:Wetting and swelling of polymer
 The wetting and swelling step occurs when the polymer spreads over
the surface of the biological substrate or mucosal membrane in order
to develop an intimate contact with the substrate.
 Swelling of polymers occur because the components within the
polymers have an affinity for water
Step 2: Interpenetration between the polymer chains and the
mucosal membrane
 The surface of mucosal membranes are composed of high molecular
weight polymers known as glycoproteins.
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 The bioadhesive polymer chains and the mucosal polymer

chains intermingle and entangle to form adhesive bonds.
 The strength of these bonds depends on the degree of
penetration between the two polymer groups.
 In order to form strong adhesive bonds, one polymer group
must be soluble in the other and both polymer types must be of
similar chemical structure.
Step 3: Formation of chemical bonds between the entangled
chains
 This step involves the formation of weak chemical bonds
between the entangled polymer chains.
 The types of bonding formed between the chains include
primary bonds such as covalent bonds and weaker secondary
interactions such as van der Waals Interactions and hydrogen
bonds. 28-Feb-19
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Theories of mucoadhesion

ADSORPTION COHESIVE

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Theories of mucoadhesion
The phenomena of bioadhesion occurs by a complex mechanism There are seven theories have
been proposed till date:
(a) The electronic theory,
Because of different electronic properties of the mucoadhesive polymer and the mucus
glycoprotein, electron transfer between these two surfaces. Electron transfer contributes to
formation of a charged double layer at the interface of the mucus and the polymer, which results in
forces of attraction in this region and inter-diffusion of the two surfaces.
(b) The adsorption theory.
Primary and secondary chemical bonds of the covalent and non-covalent (electrostatic and Van der
Waals’ forces, hydrogen, and hydrophobic bonds) types are formed upon initial contact between the
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mucus and the mucoadhesive polymer.
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(c) The wetting theory,
The wetting theory describes the ability of a bioadhesive polymer to spread on biological
surfaces. This theory is predominantly applicable to liquid bioadhesive systems.
(d) The diffusion theory
The basis of the diffusion theory is chain entanglement between glycoproteins of the mucus
and the mucoadhesive polymer.
Upon initial contact between these two polymers, diffusion of the bioadhesive polymer chain
into the mucus network creates an entangled network between the two polymers.
Sufficient polymer chain flexibility, adequate exposure for the surface contact of both
polymers, similar chemical structures, and the diffusion coefficient of the bioadhesive polymer
are among the factors which influence the inter-diffusion of the macromolecule network.
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(e) The mechanical theory
 The mechanical theory assumes that adhesion arises from an interlocking of a liquid adhesive
into irregularities on a rough surface. However, rough surfaces also provide an increased surface
area available for interaction.
(f) The cohesive theory proposes that the phenomena of bioadhesion are mainly due to the
intermolecular interactions amongst like-molecules.
(g) Fracture theory :-
 The fracture theory relates the force required for the detachment of polymers from the mucus to
the strength of their adhesive bond.
 Based on these theories, the process of bioadhesion can be broadly classified into two
categories: -Chemical method (electronic and adsorption theories)
- Physical method (wetting, diffusion and cohesive theory) 28-Feb-19
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Bioadhesion and Drug Absorption
 The drug can be incorporated into a cross linked
polymer device that would adhere to mucosal
membrane in the body.
 The adhesion of bioadhesive drugs to mucosal
membranes leads to:
- increase residence time , bioavailability & site
specificity.
- increase in the concentration of the drug at its
site of action. This means that a greater amount
of drug is available at the specific target site.
- decrease in frequency of administration with low
dose, rate of elimination.
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Oral Delivery - enhances the absorption of

drugs
- intimate contact of the dosage
Portal Circulation
form with the underlying
absorption .
- improve the therapeutic
performance of drug.
Pharmacological - controlled drug release
Response (preferably unidirectional
release).

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