1. BARRIERS OF PROTEIN BINDING
PRESENTED BY :
NISHA.N
M PHARM 1st SEM
DEPT. OF PHARMACEUTICS SUBMITTED TO :
MRS .SHEEBA .F.R
DEPT OF PHARMACEUTICS
MALLIGE COLLEGE OF
PHARMACY
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2. CONTENTS :
1) Definition
2) Why do we need to protein and peptide ?
3) Advantages and Disadvantages
4) Barriers of protein binding
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3. DEFINITION :
PROTEINS
Proteins are larger organic compounds made of amino acids and are arranged
in linear chain and are joined together by peptide bonds .
Protein > 50 amino acids
PEPTIDES
These are short polymers formed from the linking in a defined order of amino
acids .
Peptides < 50 amino acids
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4. Why do we need peptides and proteins :
The proteins and peptides are very important in biological
cells .
Lack of protein and peptides can cause a disease diabetes
mellitus .
Diabetes mellitus is caused due to the lack of protein called
‘’INSULIN’’
Now -a -days R-DNA technology and hybridoma techniques
are also used in protein and peptide based pharmaceuticals .
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5. ADVANTAGES :
1) Insulin maintains blood sugar level .
2) Oxytocin maintains labor pain .
3) Erythropoietin used for production of RBC .
4) Somatostatin decrease bleeding in gastric ulcer .
5) Gonadotrophin induce ovulation .
6) Tissue plasminogen activator is used for heart attack ,
stroke .
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6. DISADVANTAGES :
1) Very large and unstable molecules .
2) Structure is held together by weak non- covalent force .
3) Easily destroyed by relatively mild storage conditions and
gastric juices .
4) Hard to obtain in large quantities .
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7. BARRIERS TO PROTEIN AND PEPTIDE DRUG DELIVERY
1) Biological Barriers
a) Ph of biological environment
b) Enzymatic Barrier
c) Mucosal Barrier
2) Intestinal Epithelial Barrier
a) Passive and Carrier mediated transport
b) Endocytosis and transcytosis
c) Para cellular movement
3) Capillary Endothelial Barriers
4) Blood Brain Barriers ( BBB)
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8. BIOLOGICAL BARRIER
1) Ph of biological environment
The Ph conditions in various biological
environment can affect the ionization , chemical stability ,
and absorption of protein based drug and their delivery
systems .
SITE PH CAUSE
Stomach Acidic (1-3) Chemical
Degradation
Ileum and Colon Alkaline (12-14) Stable
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9. b) Enzymatic Barriers
Orally administered protein and peptide drugs
follow the same path as the ingested food in their passage
through the GI tract before being absorbed into the blood
stream from the small intestine . The enzymatic degradation is
brought about mainly via two ways :
I. Hydrolytic Cleavage of peptide bonds by processes , such as
insulin degrading enzyme , angiotensin converting enzymes
and renin . Proteolysis is an irreversible reaction and hence
potentially causes the damage of the peptide and protein drug .
II. Chemical Degradation of protein such as phosphorylation by
kinases , oxidation by xanthine oxidase or glucose oxidase . It
limits absorption of protein drugs from GI tract .
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10. Proteolytic enzyme Secreted by Function
Pepsin Gastric chief cell Break down protein
Trypsin Pancreases Break down protein
Protease Pancrease into
small intestine
Denaturation of
protein
Amylase Salivary gland Degradation of
protein
c) Mucosal Barrier
Mucus and the epithelial cell layers act as the major absorption
barrier against non-Injectable drug administration . All mucosal
epithelia are covered in a layer of mucus , which serves as the first
line of defense at the surface of the eye ,respiratory tract and GIT
against mechanical damage or the entrance of harmful substances .
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11. 2) INTESTINAL EPITHELIAL BARRIERS
a) Passive diffusion and carrier mediated gradient
The protein diffuses across the membrane in the
direction of high concentration gradient to low concentration
gradient .
Lipid soluble drugs diffuse by dissolving the lipoidal matrix of the
membrane. The rate of transport being proportional to the lipid:
water partition co-efficient of the drug .
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12. b) Endocytosis
The large molecular peptide binds to a binding protein on the
surface of the cell . The membrane invaginates to form a
vesicles which nicks off and the vesicle may remain stored
within the cell or it may disintegrate to release the substance in
the cytoplasm or be extruded across the cell by exocytosis .
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13. c) Paracellular Movement
Tight junction mediate the paracellular pathway
of absorption in intact membranes and are the rate limiting step
In transepithelial transport .Adherin junctions , which are
required for the assembly of TJ , are a multiprotein complex
made of trans-membrane proteins , peripheral membrane
proteins and regulatory molecules including kinases.
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14. 3) CAPILLARY ENDOTHELIAL BARRIER
Capillary supply the blood to most of the inner tissues .All
drugs ionized or unionized molecular size less than 600
daltons diffuse through the capillary endothelium to interstitial
fluids .
The drugs that only bind to the blood components cannot pass
through this barrier because of this larger size molecules.
Adherin junction work with desmosomes to provide the
adhesive bonds that maintain the cellular proximity and
intercellular communication .
Both adherin junction and TJ are supported by dense
perjunctional rings of actin and myosin .
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15. 4) BLOOD BRAIN BARRIER (BBB)
The capillary endothelial cells in brain have a tight junctions and
lack large paracellular space . Further , an investment of neural
tissue covers the capillaries . Together they constitute they called
as blood brain barrier (BBB).
A similar blood CSF barrier is located in the choroid plexus:
Capillaries are lined by choroidal epithelium have tight
junctions .Both these barriers are lipoidal and limit the entry of
non lipid- soluble drugs .
Only lipid soluble drugs , therefore are able to penetrate and
have action on CNS .
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18. QUESTIONS
1) Discuss the barriers associated with protein and peptide
drug delivery ? ( Nov 2022)
2) Briefly write about the barriers for the delivery of protein
and peptides ? ( July 2022)
3) Write in detail about the delivery of proteins and other
macromolecules ? (Nov 2021)
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