Department of PharmaceuticsDepartment of Pharmaceutics

BIOADHESION: Introduction, BIOADHESION: Introduction, Theories, Fundamentals And Theories, Fundamentals And

ModelsModelsPresented by: Presented by:

Gasper Fernandes(160603016)

M. Pharm 1st Year

Under the guidance Under the guidance of: of:

Dr. M. Sreenivas Reddy

CONTENTSCONTENTS

IntroductionMechanism of bioadhesionTheories of bioadhesion FundamentalsModelsConclusionReference

INTRODUCTIONINTRODUCTIONo 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.

o Type 2: Adhesion of a biological phase to an artificial substrate.

o Type 3: Adhesion of an artificial material to a biological substrate.

MECHANISMS OF MECHANISMS 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

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.

Step 2Step 2: : Interpenetration between the polymer Interpenetration 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

Step 3Step 3: : Formation of chemical bonds between the Formation 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

THEORIES OF BIOADHESIONTHEORIES OF BIOADHESION1. Wetting theoryWetting theory:oAbility of bioadhesive polymer to spread and develop intimate contact with the mucous membrane.oSpreading coefficients of polymer should be positive

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

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.

4.4. Fracture theory Fracture theory ::o Force necessary to separate two layers i.e.

mucous membrane and mucoadhesive polymer.

5. Adsorption Theory Adsorption 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.

FUNDAMENTALS OF FUNDAMENTALS OF BIOADHESIONBIOADHESION

1.1. Biological MembraneBiological Membrane::o Membranes of internal tract of body i.e. GIT,

buccal, eye, ear, nose, vagina and rectum.

• They secrete a viscous fluid known as mucus.

• Bioadhesive mucin consists of highly hydrated, cross-linked, linear, flexible and random coil glycoprotein molecule with net negative charge.

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.

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

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

4.4. Bioadhesive polymers of natural and synthetic Bioadhesive polymers of natural and synthetic sources:sources:

Natural occuring bioadhesives:• Fibronectin- Adhesive protein that binds certain

forms of collagens, glycosaminoglycans.• Lectins- Carbohydrate binding proteins and

glycoproteins and exisit on surface of mammalian cell.

Two categories:i. Integrated lectinsii. Soluble lectinsOther examples : Tragacanth, Sodium alginate

Synthetic polymers:

oCellulose derivatives: Methylcellulose, Ethyl cellulose, Hydroxy ethyl cellulose, Hydroxy propyl cellulose, Sodium carboxy methyl cellulose.oPolyacrylic acid, Polyhydroxyethyl methylacrylate, Polyethylene oxide, Polyvinyl pyrrolidone, Polyvinyl alcohol

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 mucino 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.

MODELS OF BIOADHESIONMODELS OF BIOADHESION

1. Falling liquid film method::

• 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

•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

•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

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

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.

REFERENCEREFERENCEo 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- 257-265o 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

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