2. Protein & Peptide
PROTEINS: Proteins 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
3. Functions of proteins
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
4. Importance of proteins
Erythropoietin used for production of RBC.
Tissue plasminogen activator is used for Heart attack, Stroke.
Oxytocin maintain labor pain.
Bradykinin increases the peripheral circulation.
Somatostatin decrease bleeding in gastric ulcer.
Gonadotropin induce ovulation.
Insulin maintain blood sugar level.
5. Barriers to protein drug
delivery
Enzymatic barrier limits absorption of protein
drugs from G.I. tract.
Intestinal epithelial barrier involved in the
transport of protein drugs across the intestinal
epithelium.
Capillary endothelial barrier involved in
transport of protein drugs across the capillary
endothelium.
Blood brain barrier
7. 1. Chemical modification
A chemical modification of protein and peptide drugs improves their enzymatic
stability and membrane permeation. Also it can be used for minimizing the
immunogenicity.
Prodrug approach includes.
Amino acid modification - Modification of individual amino acids by the
substitution of D- amino acid with the L-amino acid can significantly alter
physiological properties of proteins and peptides. e.g. Desmopressin and
Deaminovasopressin.
Hydrophobization - The Surface modification using the lipophilic moieties.
e.g. NOBEX INSULIN.
8. ENZYME (PROTEASE) INHIBITORS
The whole GIT and liver tend to metabolize proteins and peptides into
smaller fragments of 2-10 amino acids with the help of variety of
proteolyticenzymes.
So protease inhibitors are co-administered with proteins and peptides
to alter the environment for maximum enzyme stability to supress
proteolytic activity.
Examples of some protease enzymes : Pepsin, Papain, Thrombin,
Carboxy-peptidase.
9. PENETRATION ENHANCERS
Penetration enhancers are the formulation components that is important to
disrupt the mucosal barrier to improve the permeation of large
macromolecular substances like proteins and peptides.
Following classes of compounds are commonly used :
1. Surfactants - Polysorbate, SLS
2. Chelating agents - EDTA.
3. Fatty acids - Sodium caprate.
4. Mucoadhesive polymers - Thiomers, cellulose derivatives.
5. Phospholipids - PC.
10. FORMULATION VEHICLES
The oral delivery of therapeutic proteins and peptides can be successfully
Achieved by using various carrier systems like:
Dry emulsions (dry emulsions are prepared by drying liquid o/w
emulsions containing a solid carrier in the aqueous phase)
Cellular carriers (eg: Resealed erythrocytes)
Microspheres
Liposomes
Nanoparticles
Hydrogels (drugs enclosed in gelling polymers)
11. MUCOADHESIVE POLYMERIC SYSTEMS
These systems prevent the Pre-systemic
metabolism of the therapeutic proteins and
peptides.
Eg. Thiomers, polyacrylic acid derivatives and
cellulose derivatives.
12. Pumps
Types of Pump:
1. IMPLANTABLE PUMPS
Drug is implanted subcutaneously, and delivered by I.V infusion.
Pumps are filled with drug through a septum with a needle.
Pumps deliver drugs to central vein for 7-14 days a constant rate.
2.MECHANICALPUMPS
Easily manipulated to deliver protein and peptide drugs.
Example: insulin has been successfully delivered by portable syringe.
13. Certain Marketed formulations
Leupron
(Drug - Leuprolide : used for Prostatic cancer)
Pergonal
(FSH & LH: Used in cases of female infertility)
Calcimar
(Salmon calcitonin: Used to treat Hypercalcemia)
Acthar
(Corticotrophin: Used in cases of Hormone deficiency)
