Protein and peptides

1. Protein and peptide drug
delivery system
UNDER THE GUIDENCE OF, PRESENTED BY
DR.ANUPRIYA KAPOOR SHIVANI SINGH
ASSISTANT PROFESSOR M.PHARMA 1ST YEAR
SCHOOL OF PHARMACEUTICAL SCIENCE
CSJMU , KANPUR

2. INTRODUCTION
Protein: Proteins are the large organic compound made of amino acids
arranged in a linear chain 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

3. Why protein and peptide are used
 The protein and peptide are very important in biological
cells.
 Lack of proteins and peptides causes disease like diabetes
mellitus.
 Diabetes mellitus is caused due to the lack of protein called
INSULIN.
 Now a days R- DNA technology and hybridoma techniques
also used in protein and peptide based pharmaceuticals.

4. ADVANTAGE
 Erythropoietin is mainly used for production of RBC.
 The protein tissue plasminogen activator is used for heart
attack, stroke.
 Oxytocin is used in management of labor pain.
 Bradykinin increases the peripheral circulation.
 Somatostatin decrease bleeding in gastric ulcer.
 Gonadotropin induce ovulation.
 Insulin maintain blood sugar level.

5. DISADVANTAGE
 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.

6. 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.

7. STRUCTURE OF PROTEIN
 Primary Structure: It is a linear sequence of amino acid that
makes up polypeptide chain.
 Secondary structure : Two most common type of Secondary
structure are alpha helix and beta pleated sheet.
 Tertiary structure: It is formed by bending and twisting of the
polypeptide chain.
 Quaternary structure: Two or more polypeptide chain hold
together by non-covalent bond to give the quaternary
structure of the protein.

9. Classification of protein and peptide
 Depending on the number of amino acids they are
classified as follows:
1. Polypeptides protein
2. Oligopeptides protein
3. Fibrous protein
4. Globular protein
5. Oligo meric protein

11. Barriers to protein and peptide
delivery
The successful delivery of protein and peptide based
pharmaceuticals is primarily determined by its ability to
cross the various Barriers presented to it in the biological
milieu. Various Barriers encountered are –
 Enzymatic Barriers
 Intestinal Epithelial Barriers
 Capillary Endothelial Barrier
 Blood Brain Barrier (BBB)

12. Enzymatic Barriers
 Major Enzymatic Barrier to absorption of proteins is
pancreatic enzymes : peptidase, lipases, nucleases and
esterases.
 These are secreted in considerable quantity into the
Intestinal lumen and rapidly hydrolyses macromolecules and
lipids.
 Enzymatic degradation brought about via 2 ways
1. Hydrolytic cleavage
2. Chemical modification

13. Intestinal Epithelial Barriers
 The majority of peptide degradation occurs in the brush
border membrane.
 Brush border is microvilli covered surface of cell found in small
intestine, these plays important role in nutrient digestion and
absorption .
 Tight junctions mediate the paracellular pathway of
absorption in intact membrane and are rate limiting step in
transepithelial transport.

14. Intestinal Epithelial Barriers

15. 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. Blood Brain Barrier (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. Blood Brain Barrier (BBB)

18. Formulation vehicles
The protein and peptide drug delivery system is important
for the oral delivery of protein and peptide can be
successfully achieved by using various carrier systems
are like –
1. Dry Emulsion
2. Microspheres
3. Liposomes
4. Nanoparticles

19. Dry Emulsion
 It is important application in drug delivery system to
prevent the instabilities of the long term storage of
multiple emulsions.
 The novel approach at which multiple emulsion is
replaced by dry emulsions.
 In dry emulsion preparation application of the PH
responsive polymers like HPMC, is important for the
emulsion are the enteric coated and sites specific
achieved.

20. 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 degradation and protection upper portion
of small intestine from proteolytic degradations

21. 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.

22. 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
degradation.
 The particle size surface charges are the influencing the
uptake of nanoparticle system in GI tract.

23. Evaluation of protein and peptide drug
formulation
 Stability testing
 Bioassay
 UV spectroscopy
 Bradford assay
 Differential scanning calorimetry
 Chromatography
 Electrophoresis

24. Reference
 Bruno BJ, Miller GD,Lim CS.Basics and recent advances in
peptide and protein drug delivery. Therapeutic delivery.
2013;4(11):1443-1467.doi:10.4155/tde.13.104
 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2792531/
 Sagar kishor savale,protein and peptide drug delivery
system, world journal of pharmacy and pharmaceutical
sciences, 5,724-742,2016
 https://study.com/academy/lesson/primary-structure-of-
protein -definition-lesson-quiz.html