PROTEINS: Proteins are the organic compounds made of amino acids and joined together by peptide bonds. PEPTIDES: These are short polymers formed from the linking in a defined order of amino acids. Protein and peptides are the most abundant material which act as hormones, transport protein, structural protein, receptor, immunoglobulin’s in living system and biological cell. Protein and peptides are important part in several metabolic process, immunogenic defense and many other biological activities. Protein and peptide use in the treatment of various diseases including Endocrine dysfunction, Infection diseases, Cancer, and CNS disorders. According to their biological roles Enzymes- Catalyses virtually all chemical reaction Transport proteins i.e. Haemoglobin of erythrocytes Defense proteins i.e. Immuno globulins Antibodies Structural proteins i.e. Collagen in bones Regulatory proteins i.e. insulin Nutrient and storage proteins i.e. ovalbumin According to their solubility Globular proteins: Soluble in Water Fibrous proteins: Insoluble in water WHY PROTEN AND PEPTIDE DRUGS? The protein and peptide are very important in biological cells. Lack of proteins and peptides causes diseases like Diabetes mellitus. Diabetes mellitus is cause due to the lack of protein called INSULIN. Now a day R-DNA technology and hybridoma also use in protein and peptide based pharmaceuticals. FUNCTIONS Transport and storage of small molecules. Coordinated motion via muscle contraction. Mechanical support from fibrous protein. Generation and transmission of nerve impulses. Enzymatic catalysis. Immune protection through antibodies. Control of growth and differentiation via hormones. Problems with proteins Elimination by B and T cells. Proteolysis by endo/exo peptidases. Small proteins filtered out by the kidneys very quickly. Unwanted allergic reactions may develop (even toxicity). Loss due to insolubility/adsorption.

1. PROTEN AND PEPTIDE DRUG DELIVERY SYSTEM
UNDER THE GUIDENCE,
OF
Dr. Lalit Kumar Tyagi
M. Pharm, Ph.D.
Presented By
Girdhar kumar Sahu
M. Pharm 1st Yr
Department of pharmaceutics
Lloyd Institute of Management
and Technology [PHARM.]

2. CONTENTS
 Protein and peptides
 Classification of protein
 Properties of proteins and peptides
 Stability problems
 Barriers to protein drug delivery
 Drug delivery system
 Stability testing
 References

3. INTRODUCTION
PROTEINS: Proteins are the organic compounds
made of amino acids and joined together by peptide
bonds.
PEPTIDES: These are short polymers formed from
the linking in a defined order of amino acids.
 Protein and peptides are the most abundant material
which act as hormones, transport protein, structural
protein, receptor, immunoglobulin’s in living system
and biological cell.

4. Cont..
Protein and peptides are important part in several
metabolic process, immunogenic defense and many
other biological activities.
Protein and peptide use in the treatment of various
diseases including Endocrine dysfunction, Infection
diseases, Cancer, and CNS disorders.

5. CLASSIFICATION OF PROTEINS
According to their biological roles
Enzymes- Catalyses virtually all chemical reaction
Transport proteins i.e. Haemoglobin of erythrocytes
Defense proteins i.e. Immuno globulins Antibodies
Structural proteins i.e. Collagen in bones
Regulatory proteins i.e. insulin
Nutrient and storage proteins i.e. ovalbumin
According to their solubility
Globular proteins: Soluble in Water
Fibrous proteins: Insoluble in water

6. WHY PROTEN AND PEPTIDE DRUGS?
The protein and peptide are very important in
biological cells.
Lack of proteins and peptides causes diseases like
Diabetes mellitus.
Diabetes mellitus is cause due to the lack of protein
called INSULIN.
Now a day R-DNA technology and hybridoma also use
in protein and peptide based pharmaceuticals.

7. FUNCTIONS
Transport and storage of small molecules.
Coordinated motion via muscle contraction.
Mechanical support from fibrous protein.
Generation and transmission of nerve impulses.
Enzymatic catalysis.
Immune protection through antibodies.
Control of growth and differentiation via hormones.

8. ADVANTAGES
Erythroprotein used for production of RBC.
Tissue plasminogen activitor is used for heart attack,
stroke.
Oxytocin maintain labor pain.
Somatostatin decrease bleeding in gastric ulcer.
Gonadotropin induce ovulation.
Insulin maintain blood sugar lever.

9. DISADVANTGES
Very large and unstable molecules.
Easily destroyed by relatively mild storage condition
and gastric juices.
Hard to obtain in large quantities.

10. PROPERTIES OF PROTEEINNS AND PEPTIDES
 Molecular size weight of protein: The large
molecular weight have low diffusivity and small
molecule (75-100 dalton) cross barrier.
 Stereo-specificity, Conformation: Affects the
permeability.
 Solubility and partition coefficient: Peptides are very
hydrophilic, so to improve the absorption of peptides
by passive diffusion, their lipophilicity should be
increased.

11. PROBLEMS WITH PROTEINS
Elimination by B and T cells.
Proteolysis by endo/exo peptidases.
Small proteins filtered out by the kidneys very quickly.
Unwanted allergic reactions may develop (even
toxicity).
Loss due to insolubility/adsorption.

12.  Enzymatic Barrier
 Intestinal Epithelial Barrier
 Capillary Epithelial Barrier
 Blood Brain Barrier
BARRIERS TO PROTEIN DRUG
DELIVERY

13. ENZYMATIC BARRIERS
 • 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 renin. Proteolysis is an
irreversible reaction and hence potentially causes the
of damage of the peptide and protein drug.
 2.Chemical modification of protein such as
phosphorylation by kinases, oxidation by xanthine-
oxidase or glucos oxidase.
 It limits absorption of protein drugs from G.I tract

14. INTESTINAL EPITHELIAL BARRIER
 Intestinal epithelial barrier Serves as a barrier for
transport of protein drugs across the intestinal
epithelium.
 Several mechanisms that are involved in the transport
of peptide /protein drugs across the intestinal
epithelium are
 A. Passive & carrier mediated transport
 B. Endocytosis & Transcytosis
 C. Paracellular Movement

15. A. Passive and carrier mediated transport:
 Active transport appears to be the predominant mechanism. Accounts
for the extensive absorption of di-and tripeptides from small
intestine.
B. Endocytosis and transcytosis
 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 involve Phagocytosis
Pinocytosis (cell drinking).
C. Paracellular movement:
 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 (insulin) 2.Persorption
 The small intestine epithelial mucosa serves as a barrier to the
permeation of macromolecules

16. CAPILLARY ENDOTHELIAL BARRIER
 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. BLOOD BRAIN BARRIER (BBB)
 The blood-brain barrier (BBB) represents a major obstacle
to the delivery of proteins to the brain compartment. It
consists of several barriers with the two that are best
described being the vascular BBB, and the blood-
cerebrospinal fluid (blood-CSF) barrier.
 At both sites, the BBB is formed by a monolayer of cells
that are cementedtogether by tight junctions and have other
mechanisms that control or retardleakage of plasma into the
CNS.
 Allows passage of small, lipophilic, uncharged molecules
and gases. Large molecules like proteins do not pass the
BBB easily

18. PHARMACEUTICALAPPROACHES
OF PROTEIN AND PEPTIDES
 CHEMICAL MODIFICATION
 ENZYME INHIBITORS
 PENETRATION ENHANCERS
 FORMULATION VEHICLE
 MUCOADHESIVE POLYMERIC SYSTEM

19. 1. CHEMICAL MODIFICATION (PRODRUG
APPROACH)
 The Chemical Modification of Protein and Peptide Drug
Delivery System of Drugs is Important to Improve the
Enzymatic Stability as well as Membrane Permeations.
 It is Applicable for the reducing the Immunogenicity.
 The Chemical Modification is Includes in Two Types of
Modifications
1. Amino acid Modification: The Modification of amino acid
is one of the important approach in which the Substitution of
the D- amino acid and L- amino acid is important to alter the
Physiological Properties of Protein and Peptide Drug
Delivery Systems
2. Hydrophobization: It is having an important approach for
the Lipophilic Moieties

20. 2. ENZYME INHIBITORS (PROTEASE): The enzyme
(protease) inhibitors are the enzymatic approach of the
Protein a
3 . PENETRATION ENHANCERS: Penetration enhancers
are the one of the most important Component of Protein and
Peptides formulation is responsible for the Disruption of the
Mucosal Barriers and applicable to improve the Membrane
Permeations of Large Macromolecular substances lie
Proteins and Peptides.
4 . FORMULATION VEHICLES: The Protein and Peptide
Drug Delivery system is important for the Oral Delivery of
Protein and Peptides can be successfully achieved by using
various carrier systems are like 1. Dry Emulsion 2.
Microspheres 3. Liposomes 4. Nanoparticles

21.  1. Dry Emulsion is prepared by the Spray drying,
Lyophollization and evaporation Techniques. In dry emulsion
preparation application of the PH responsive polymers like
HPMCP, is important for the emulsions are the enteric coated
and site specific achieved.
 2. Microspheres: The uniform distribution of drug in oral
drug delivery in Protein peptides drug are known as
Microspheres. The PH responsive microspheres are the
mainly used in oral delivery for the protection of the stomach
from proteolytic degradations and Protection upper portion of
small intestine from proteolytic degradations.

22.  3. Liposomes: Liposomes are the small microscopic vesicles
in which aqueous volume is entirely enclosed by the
membrane composed lipid molecules. Liposomes in drug
delivery system, the encapsulation of the insulin with sugar
chain portion of mucin and PEG completely suppressed the
degradation of the insulin molecules in intestinal fluid. The
uncoated from of liposomes are suppressed it on partially
surface coating of the liposomes molecules in PEG or mucin
gained resistances against dagestion by salts and increased
the stability of GI tract.
 4. Nanoparticles: Nanoparticles are Nano sized colloidal
structure having size is 10-1000nm. The particles in
nanometric sized range of the particles are absorbed intact by
the intestinal epithelium and they are the less prone towards
the enzymatic degradations. The particle size surface charges
are the influencing the uptake of nanoparticle system in GI
tract.

23. 5. MUCOADHESIVE POLYMERIC
SYSTEMS
The mucoadhesive polymeric system is important to prevent the
problem associated in Presystemic Metabolism or first pass
metabolism and maintain its therapeutic efficacy. The residence
time of this drug delivery systems at the site of action and the
increasing or decreasing the drug clearance rate.

24. STABILITY ASPECTS
In stability of protein and peptide is determined by the Protein degradations
PathwaysIn This drug delivery system under two Pathways of
degradation of Protein and Peptide Molecules
1.Physical Degradation Pathways (Instability Aspects)
2.Chemical Degradation Pathways (Instability Aspects)
1. Physical Instabilities: The Physical Degradation Pathways the Native
or original structure of Protein is Changes or Modified to from Higher
order Structure of Proteins (secondary, tertiary or quaternary structure).
2. Chemical Instabilities: Chemical degradation Pathways the Native or
original structure of protein is changes by the modification of their
Primary Structure of Protein Molecules.The chemical instability of the
protein and Peptide can causes following four types of reactions.
3. Oxidation
4. 2. Deamination
5. 3. Peptide bond hydrolysis
6. 4. Disulphide exchange

25. APPLICATION
 1. CVS acing drugs Protein and Peptides
 CNS active Protein and Peptides
 GI-active Protein and Peptides
 Immunomodulation of the Protein and Peptides
 Metabolism modulating Protein and Peptides

26. REFERENCE
 Sagar Kishor Savale, Protein and peptide drug delivery
system, world journal of pharmacy and pharmaceutical
sciences, Vol 5, Issue 4, 2016
 A text book of drug delivery system, Prafull P.Patil pg.
189-216.
 P. keerthi, Protein and peptide drug delivery system,
201 4.

27. Thankyou!