Proteins and peptide drug delivery system

1. PROTEIN AND PEPTIDE
DELIVERY SYSTEM
PRESENTED BY :
Ms. Mrinal R. Gite
M. PHARM 1st YEAR
ROLL NO: 04
(Department of Pharmaceutics)
Rajarshi Shahu College Of Pharmacy, Buldana.443001
GUIDED BY: Dr. P. N. Kendre
HOD, Department of Pharmaceutics
1

2. CONTENTS
➢ Introduction
➢ Structure Of Proteins And Peptides
➢ Barriers For Protein Delivery
➢ Delivery Of Protein And Peptide Delivery
➢ Conclusion
5/11/2020 2

3. INTRODUCTION
▪ Proteos - holding 1st Place.
▪ High molecular weight compounds Containing linear chain of
amino acids , joined together by covalent bond.
▪ Protein – Molecule composed of over 50 amino acids.
▪ Peptide – Molecule composed of less than 50 amino acids.
▪ Important role in Oxygen and CO2 transport by Haemoglobin in
RBCs.
5/11/2020 3

4. 5/11/2020
4
STRUCTURE OF PROTEIN AND PEPTIDES
▪ Essential to have an idea about the structure of protein and
peptides in order to deal with various problems comes while
developing the DDS.
▪ They adopt 3D pattern and confirmation.
▪ These are polymers of amino acids connected via amide linkage
called “ Peptide Bonds”.

5. 5/11/2020 5
Primary Structure
▪ Not rigid instead flexible because of nature of bonds that holds
amino acids together.
▪ Denotes no. And specific sequence of amino acids.

6. 5/11/2020 6
Secondary Structure
▪ Arrangement of individual amino acid along with Polypeptide
backbone.
Alpha helix Beta sheet

7. 5/11/2020 7
Tertiary Structure
▪ 3D Arrangement of single protein molecule due to intermolecular
interaction between side groups along the polypeptide chain.
▪ Its domain typically contains 300-400amino acids and adopts
stable structure when it is isolated from parent protein.

8. 5/11/2020 8
Quaternary Structure
▪ That contains two or more polypeptide chains associated
by non-covalent forces.
▪ Eg : hemoglobin - 2 alpha & 2beta subunits.

9. 5/11/2020 9
BARRIERS FOR PROTEIN DELIVERY
1.Enzymatic Barrier
2.Intestinal Epithelial Barrier
3.Capillary Endothelial Barrier
4.Blood Brain Barrier
1.Enzymatic barriers
▪ Major enzymatic barrier to absorption of proteins is pancreatic
enzymes: peptidase,lipases,nucleases & esterases.

10. 5/11/2020 10
▪ These are secreted in considerable quantity into the intestinal
lumen and rapidly hydrolyses macromolecules and lipids.
Peptidase – they work in coordinated fashion, where by the
action of pancreatic enzymes is augmented by those in the
brush border of the intestinal cells
Mucosal cells slugg off into lumen mix.
Of enzymes is furnished which is threat to
macromolecules.

11. 5/11/2020 11
Enzymatic degradation brought about via 2 ways
1.Hydrolytic cleavage of peptide bonds by Insulin degrading
enzyme, ACE & Renin .
▪ Proteolysis is irreversible reaction and hence causes damage of
peptides and protein drugs.
2.Chemical modification of protein such as phosphorylation by
kinases,oxidation by xanthine oxidase or glucose oxidase.
▪ It limits absorption of protein drugs from GIT.

12. 5/11/2020 12
2.Intestinal Epithelial Barrier
▪ The majority of peptide degradation occurs in the brush border
membrane.

13. 5/11/2020 13
▪ Brush border is microvilli covered surface of cell found in small
intestine,these plays imp.role in nutrient digestion and
absorption.
▪ Tight junctions mediate the paracellular pathway of absorption
in intact membranes and are rate limiting step in transepithelial
transport.

14. 5/11/2020 14
▪ Adherens junctions required for assembly of (TJs) & are
multiprotein complex made of trans membrane proteins,
peripheral membrane proteins and regulatory molecules including
kinases.
▪ Both the junctions are supported by dense perijunctional rings of
Actin and Myosin.
▪ Adherens junction works with Desmosomes to provide the
adhesive bands to maintain cellular proximity& intercellular
communication.

15. 5/11/2020 15
3.Capillary Endothelial Barrier
▪ To cross capillary endothelium the proteins must pass between
cells or alternatively transverse the endothelial cells themselves.
▪ Solutes that transverse endothelial cell membrane may get
metabolised by cytoplasmic enzymes.
▪ Thus the endothelial passes enzymatic barrier to solution package.

16. 5/11/2020 16
4.BBB
▪ Represents major obstacal to brain compartments.
▪ Collection of cells that press together to block many substances
from entering the brain while allowing other to pass.
▪ Allow passage to lipid mediated transport of small but lipophilic
molecules and gases.
▪ Large molecules like proteins donot pass the BBB early.

17. 5/11/2020 17
DELIVERY OF PROTEINS AND PEPTIDE DRUGS
1.Oral route
2.Buccal route
3.Nasal route
4.Occular route
5.Rectal route
6.Transdermal route
7.Parenteral route
8.Pulmonary route

18. 5/11/2020 18
Route of
Administration
Advantages Barriers Advantages of polymeric
NPs
Oral
• High patient
compliance
• Low permeability
through GIT epithelia
• Degradation by
proteolytic enzymes
• Instability at acidic
pH in stomach
• Enhancement of oral
absorption
• Improved bioavailability
• Prolonged residence time
in the intestine
• Sustained drug release
• Enhanced stability in the
GIT

19. 5/11/2020 19
Route of
Administration
Advantages Barriers Advantages of
Polymeric NPs
Nasal
•Highly vascularized
mucosa
•Porous endothelial
membrane
•lower enzymatic
activity
•Direct brain delivery
•Avoidance of first-
pass metabolism
• Mucociliary
clearance
• Improved
systemic and
brain absorption
• Sustained release
• Minimal
enzymatic
degradation of
encapsulated
proteins

20. 5/11/2020 20
Route of
Administration
Advantages Barriers Advantages of polymeric
NPs
Ocular
• Ease of
administration
• Avoidance of
first-pass
metabolism
• Poor
permeability
• Enzymatic
degradation
• Nasolacrimal
drainage
• Protection from
enzymatic degradation
• Prolonged residence time
in cul-desac
• Lower drug loss due to
tear turnover
• Sustained drug release

21. 5/11/2020 21