Intro,barriers,adv,etc

1. PRESENTED BY
AISHWARYA C. PATIL
M. PHARM (FIRST YEAR)
DEPT.OF PHARMACEUTICS
RAJARAMBAPU COLLEGE OF PHRMACY KASEGAON

2.  The term “Protein” is derived from a Greek
word Proteios - means holding the first place.
 The high molecular weight compound
containing a Nitrogen rich most abundant
substances present in animals and plants
system.
 Proteins are the linear chains of amino acids
that are held together by covalent linkages
called “ Peptide bonds”.
 Protein is play major part in Transport of
Oxygen and Carbon dioxide by Hemoglobin
Present in Red blood cells.

3.  Proteins: These are the large organic
compounds made of amino acids arranged in
a linear chain and 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. peptide < 50 amino acids

4.  The protein and peptides are very important
in biological cells.
 Lack of proteins and peptides causes
diseases like Diabetes mellitus.
 Diabetes mellitus is caused due to the lack
of protein called INSULIN.

5.  Erythropoietin used for production of RBC.
 Tissue plasminogen activator is used for
Heart attack, Stroke.
 Oxytocin maintain labor pain.
 Somatostatin decrease bleeding in gastric
ulcer.
 Insulin maintain blood sugar level.

6.  Very large and unstable molecules.
 Structure is held together by weak non-
covalent forces.
 Easily destroyed by relatively mild storage
conditions and gastric juices.
 Hard to obtain in large quantities.

7.  Depending on the number of amino acids
they are classified as follows:
 Polypeptides
 Oligo peptides
 Fibrous proteins
 Globular proteins
 Oligomeric proteins

8.  1. Enzymatic barriers
 2.Intestinal Epithelial Barrier
 3.Capillary Endothelial Barrier
 4.Blood Brain Barrier(BBB)

9. The enzymatic degradation is brought about mainly via two ways:
1.Hydrolytic cleavage of peptide bonds by processes, such as
insulin-degrading enzyme, angiotensin-converting enzymes
and rennin.
Proteolysis is an irreversible reaction and hence potentially
the probability of damage of the peptide and protein drug.
2.Chemical modification of protein such as phosphorylation by
kinases, oxidation by xanthine oxidase or glucose oxidase.
These chemical changes in the substrate protein are reported
to affect the rate and site of hydrolysis catalyzed by processes,
thus the peptide/protein become more susceptible to
proteolytic attacks.

10.  The several mechanisms that are involved in
the transport of peptide /protein drugs
across the intestinal epithelialium.
 A. Passive & carrier mediated transport
 B. Endocytosis & Transcytosis
 C.Paracellular Movement.

12. A. Passive and carrier mediated
transport :
 The extensive absorption of di-and tri-
peptides from small intestine. Active
transport appears to be the predominant
mechanism.
 there is little evidence that peptides with
more than three or four amino acid residues
are transported across the intestinal mucosa
by the peptide transport
system.sterioisomerism, side-chain length,
and N-and C-terminal substitution are
reported to affect dipeptide absorption.

13.  Cellular internalization of peptides/proteins
may occur by Endocytosis whereby peptide
/proteins, which are too large to be absorbed
by carrier mediated transport, are taken up.
 The Different pathways of Endocytosis
 1.Phagocytosis(cell eating) :absorption uptake
of solid particulates.
 2.Pinocytosis(cell drinking) :uptake of fluid
Solutes.
 The small intestine epithelial mucosa serves as
a barrier to the permeation of
macromolecules.

15.  The transport of drugs through the junction
between the GI epithelial cells.
 Two mechanism involved in drug absorption
are-1.Permeation through tight junction of
epithelial cells, 2.Persorption
 Paracellular Movement plays an important
role in the absorption of water from the
intestinal lumen.

16.  To cross the capillary endothelium the
peptides/proteins must pass between the cells
or alternatively transverse across the
endothelial cells themselves.
 Solutes that transverse the endothelial cell
membrane may get modified or metabolized by
cytoplasmic enzymes.
 Thus, the endothelial passage poses metabolic
or enzymatic barrier to the solution passage.

17.  The blood-brain barrier(BBB) is a collection of
cells that press together to block many
substances from entering the brain while
allowing other to pass.
 Different mechanisms for their transport across
BBB
 Lipid mediated transport of small but lipophilic
molecules
 Plasma protein mediated transport of acidic
drugs, peptides and highly lipophilic drugs.