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Bioadhesion
1. Department of PharmaceuticsDepartment of Pharmaceutics
BI OADHESI ON: I nt roduct ion,BI OADHESI ON: I nt roduct ion,
Theories, Fundament als And ModelsTheories, Fundament als And Models
Presented by:Presented by:
Gasper Fernandes
(160603016)
M. Pharm 1st
Year
Under the guidance of:Under the guidance of:
Dr. M. Sreenivas Reddy
3. INTRODUCTIONINTRODUCTION
o Bioadhesion: Adhesion between two materials, one
biological in nature, are held together by interfacial
forces.
o Mucoadhesion: Adhesion of polymer to mucosal
membrane.
ClassificationClassification
oType 1: Adhesion between
two biological phases.
4. o Type 2: Adhesion of a
biological phase to an
artificial substrate.
o Type 3: Adhesion of an
artificial material to a
biological substrate.
5. MECHANISMS OFMECHANISMS OF
BIOADHESIONBIOADHESION
I. Wetting and swelling of polymer
II. Interpenetration between the polymer
chains and the mucosal membrane
III. Formation of chemical bonds between the
entangled chains
6. Step 1Step 1:: Wetting and swelling of polymerWetting and swelling of polymer
o 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.
7. Step 2Step 2:: Interpenetration between the polymerInterpenetration between the polymer
chains and the mucosal membranechains and the mucosal membrane
The bioadhesive polymer chains and the mucosal
chains intermingle and entangle to form semi
permeable adhesive bonds. The strength of these
bonds depends on the degree of penetration
between the two groups.
Bioadhesive
polymer chains
Mucus chains
8. Step 3Step 3:: Formation of chemical bonds between theFormation of chemical bonds between the
entangled chainsentangled chains
This step involves the formation of weak chemical
bonds between the entangled polymer chains.
Primary bonds such as covalent bonds and weaker
secondary interactions such as Vander Waals
Interactions and hydrogen bonds
9. THEORIES OF BIOADHESIONTHEORIES OF BIOADHESION
1. Wetting theoryWetting theory:
oAbility of bioadhesive polymer to spread and
develop intimate contact with the mucous
membrane.
oSpreading coefficients of polymer should be
positive
10. 2.2. Diffusion theoryDiffusion theory:
o Time dependent diffusion of polymeric chains
into glycoprotein chain of mucous.
o The exact depth to which the polymer chains
penetrate the mucus depends on the diffusion
coefficient and the time of contact
11. 3.3. Electronic TheoryElectronic Theory:
o Electronic transfer occur because of differences
in their electronic structure.
o Formation of an electronic double layer at the
interface & adhesion occurs due to attractive
forces across the double layer.
12. 4.4. Fracture theoryFracture theory ::
o Force necessary to separate two layers i.e.
mucous membrane and mucoadhesive polymer.
13. 5. Adsorption TheoryAdsorption Theory ::
oMaterials adhere because of surface forces acting
between the atoms in the two surfaces.
oTwo types of chemical bonds such as primary
covalent and secondary chemical bonds are
involved in the adsorption process.
15. ā¢ They secrete a viscous fluid known as mucus.
ā¢ Bioadhesive mucin consists of highly hydrated,
cross-linked, linear, flexible and random coil
glycoprotein molecule with net negative charge.
16. 2.2. Bioadhesive PolymersBioadhesive Polymers:
o A bioadhesive polymer is a synthetic or natural
polymer which binds to biological substrates
such as mucosal membrane.
I.I. ClassificationClassification:
a) Polymers that are water soluble, linear and
random polymers. E.g. Sodium CMC, HPC.
b) Water insoluble polymer that are swellable
networks joined by cross linking network. E.g.
carbopol.
17. II.II. PropertiesProperties:
a) Molecular weight: Bioadhesive strength increase
above 100,000.
b) Cross linking density: Decreases diffusion
coefficient, chain segment flexibility and mobility
thereby reducing extent of penetration.
c) Charges and ionization: Polyanionic polymers are
preferred over polycationic and neutral polymers.
d) Hydrophilic group and hydration: Secondary bond
formation, expand the gel to create pores and
mobilize chains for interpenetration
18. 3.3. Bioadhesion at exposed epithelial surfaceBioadhesion at exposed epithelial surface::
o Maintains continuity of mucous layer
o Provides a protective covering for the underlying
cell layers from physical and chemical stress.
o Acts as a platform for drug delivery to local tissues
and facilitates recovery of the damaged or
diseased cell layers.
e.g. Sucralfate, adhere selectively to ulcer and
eroded surface of epithelial cell by electrostatic
attraction
19. 4.4. Bioadhesive polymers of natural and syntheticBioadhesive polymers of natural and synthetic
sources:sources:
Natural occuring bioadhesives:
ā¢ Fibronectin- Adhesive protein that binds certain
forms of collagens, glycosaminoglycans.
ā¢ Lectins- Carbohydrate binding proteins and
glycoproteins and exisit on surface of mammalian
cell.
Two categories:
i. Integrated lectins
ii. Soluble lectins
Other examples : Tragacanth, Sodium alginate
21. 5.5. Modulation of MucoadhesionModulation of Mucoadhesion:
o Substances like tetracyclins, progesterone, interact
with mucin to cause either mucin thickening or
thinning.
o Calcium precipitates mucin
o Degree of hydration of mucoadhesive decreases
with increase in ionic strength of media.
o Mucolytic agents reduce viscosity of mucous.
o Structural breakdown of mucous by adding sodium
deoxycholate and lysophosphatidyl choline.
o Disease state also disrupts integrity of mucin
network.
22. MODELS OF BIOADHESIONMODELS OF BIOADHESION
1. Falling liquid film method::
ā¢ The adhesion of particles to
the surface is measured by
passing the particle
suspension over the
surface and by comparing
the fraction of particles
adhered to the tissue
23. ā¢Prepared tablets were attached intestinal porcine
mucosa spanned on stainless steel cylinder which
was placed in the dissolution apparatus containing
100Mm (TBS) and was agitated with 250 rpm. The
detachment, disintegration or erosion of tablet were
observed and recorded within a time period of 10h.
2. Study of mucoadhesive strength using
USP apparatus 4
24. ā¢A modified balance method used where goat
buccal mucosa was model substrate and
phosphate buffer pH 6.8 used as the moistening
fluid. The tablet was laid onto the model
membrane and bioadhesive strength was
measured in terms of weight in grams of water
required to detach the tablet from the goat buccal
mucosa.
3. Ex vivo mucoadhesive strength
25. The fresh goat buccal mucosa was tied on the
glass side, and a mucoadhesive core side of each
tablet was wetted with phosphate buffer pH 6.8
and attached to glass slide. The glass slide was
then put in the beaker containg 200 mL of the
phosphate buffer pH 6.8 The time for detach of
tablet from the goat buccal mucosa was recorded
as the mucoadhesion time
4. Ex vivo mucoadhesion time
26. CONCLUSIONCONCLUSION
Bioadhesion can be beneficial, as it can facilitate
the desired adhesion of cells and biomolecules
on various natural and synthetic substrates,
which then leads to the development of novel
biomaterials, therapies and technologies such as
biosensors.
27. REFERENCEREFERENCE
o Rao NR, Shravani B, Reddy MS. Overview on buccal drug
delivery systems. J. Pharm. Sci. & Res. 2013;5(4):80-88.
o Vyas S. Khar R. Controlled drug delivery- Concepts and
advances. 2nd ed. Delhi; 2016.Pg no- 257-265
o Mathiowitz E, Chickering III DE, Lehr CM, editors. Bioadhesive
drug delivery systems: fundamentals, novel approaches, and
development. CRC Press; 1999 Jul 13.Pg no. 1-8.
o Lenaerts VM, Gurny R. Bioadhesive drug delivery systems.
CRC Press; 1989 Nov 30.Pg. no. 67
o Bhushan B. Biomimetics: bioinspired hierarchical-structured
surfaces for green science and technology. Springer; 2016
Mar 22.Pg. No. 23